0099-2399/90/1602-0098/$02.00/0 JOURNAL OF ENDODONTICS Copyright 9 1990 by The American Assooat~on of Endodontlsts
Printed in U.S.A. VOL. 16, NO 2, FEBRUARY1990
Pathogenic Mechanisms in Pulpal Disease Gunnar Bergenholtz, DDS, Odont. Dr.
The unpredictable response of the dental pulp to clinical insults is frequently encountered in the daily practice of dentistry. Even though the pulp often shows remarkable capacity for recovery, painful symptoms and pulp tissue breakdown may follow such clinical insults as caries, dental trauma, or operative dental procedures. In recent years pulp biology research has provided a deeper insight into the basic mechanisms that govern pulpal defense and repair. This communication focuses on dentin permeability to bacterial antigens and how bacterial elements may be processed and dealt with by the dentin-dental pulp complex.
other hand, pulpal tissue healing and hard tissue repair consistently occurred in spite of the fact that the palpal exposures were filled with food debris, hair, and other matter (i). Bacterial influences are also highly significant in the pathogenesis of pulpal inflammatory lesions under dental restorations. Experimental studies in humans and animals carried out over the past 15 yr have shown a strong association between pulpal lesions and marginal leakage of bacteria, while dental restorative materials per se cause little or no irritation of the pulp provided marginal leakage has been effectively prevented (for review see ref. 3). Very recently, Cox et at. (4) added strong support for the concept of bacterial influences being a major factor in the development of puipal lesions following restorative therapy. They investigated in monkeys the direct effect of a variety of common dental materials on the pulpal tissue. Through Class V cavity preparations they exposed the pulp and placed the restorative materials over the exposure site. To prevent marginal leakage, the outer portion of the restoration was removed and substituted with zinc-oxide eugenol cement according to the method designed by Br~innslrdm and Nyborg (5). In control cavities no such surface seal was conducted. Histological findings 3 wk after the initiation of the experiment showed pulp tissue reorganization and hard tissue repair with silicate cement, composite, and zinc phosphate cement restorations. This type of healing was observed only in teeth where a zinc oxide-eugenol cement surface seal had been placed. On the other hand, severe inflammation and necrosis were noted under restorations without a surface seal. In these latter teeth bacteria were often found at the pulp tissue-restoration interface. A large number of investigations carried out during the past 15 to 25 yr implicate bacterial infection as a most important factor in pulpal disease pathogenesis. It is obvious that it is from this basis that the answers to the sometimes erratic behavior of the pulp to clinical injury and painful events should be sought.
The connective tissue of the dental pulp is located in a very special environment. It is surrounded by a tough encasement of hard tissue, i.e. dentin, cementum, and enamel that normally provides strong mechanical support and protection. As long as this hard tissue barrier is intact, the pulp will not be exposed to adverse influences from injurious elements present in the oral environment, and it will under this condition remain in a healthy and functional slate. However, in a number of clinical situations well known to the dentist (Table l), teeth suffer the loss of hard tissue integrity. When the outer enamel or cementum layers are broken through, the potential exists for noxious components in the oral environment to gain access to the pulp and adversely influence the tissue along exposed dentinal tubules. I M P A C T OF T H E ORAL M I C R O B I O T A In the oral cavity a number of elements are present which potentially can be injurious to the pulp. It is now well documented that bacteria and bacterial by-products are associated with most pulpal disease processes and that, for example, food items and components from restorative materials in common use in dentistry today, play relatively insignificant roles. The classical experiments by Kakehashi et al. (I, 2) laid essential groundwork for our current concepts regarding the impact of the oral microbiota in palpal disease and demonstrated in conventional and germ-free rats that bacterial infection is a key factor. After exposure of pulps to the oral environment, they observed palpal necrosis and periapical abscesses in conventional rats. In the germ-free rats, on the
PERMEABILITY OF DENTIN TO BACTERIAL ANTIGENS A critical question is whether a walt of dentin separating the pulp from the oral environment can provide protection of the pulp against bacterial influences. Experiments have demonstrated that although dentinal tubules can be invaded by oral microorganisms after bacterial plaque accumulation, bacterial penetration of noncarious dentin to the pulp is a rare finding even after long-term exposure of dentin to the 98
Vol. 16, No. 2, February 1990
Mechanisms of Pulpal Oiseese
TABLE 1. Major etiological factors of pulpal disease Microbial Caries Periodontal disease
Traumatic
latrogenic
Concussion/luxation injuries Crown/root fractures
Trauma from operative procedures Marginal leakage Dental material toxicity
oral microflora (6). However, during clinical procedures one can facilitate bacterial invasion of the pulp by eliminating the smear layer and opening up the tubular orifices by acid etch procedures before restoration. If dentinal tubules have not been properly blocked or covered by a base material or liner and if the subsequent restoration has a poor marginal adaptation, bacteria may gain direct access to the pulp. Even though oral microorganisms, in general, have limited capacities to invade the pulp along dentin, it is clear from a number of experimental studies that dentin is not an effective barrier against the diffusion of bacterial components. In a series of experimental studies carried out in our laboratory (7-11 ), we have employed an experimental model that made use of Class V cavities preparations in teeth of monkeys or humans. These cavities were used to test the influence on the pulp of bacterial substances of various types after their topical application to fresh preparations of dentin. These experiments have demonstrated that the dentin-dental pulp complex responds rapidly to bacterial challenges. Findings also suggest that a thin wall ofcoronal dentin is unable to prevent bacterial substances, including high molecular weight complexes of bacterial cell walls, from adversely affecting the underlying pulp. Even the presence of a smear layer does not seem to prevent the diffusion of bacterial substances along the dentinal tubules, since in none of our experiments were attempts made to remove this debris by EDTA or acids. Based on these findings it is reasonable to conclude that fresh exposures of dentin are highly permeable to bacterial elements present in saliva or released from bacterial plaques. One must remember, however, that in none of our experiments have we proven that bacterial components actually are being transported through dentin to the pulp, where the inflammatory responses are induced. In other words, it may be that bacterial elements do not penetrate at all or just enter the dentin a short distance. Thus, the potential exists that the initial reactions of the host defense including the migration of polymorphonuclear neutrophils are initiated through the activation of some form of host defense mechanism present within the dentinal fluids. This implies that inflammatory lesions, developing in the pulp in response to bacterial irritation of exposed dentin, may be initiated either by the diftusion of bacterial elements and/or the activation of signal substances released from the dentinal fluids. CHANGES IN D E N T I N PERMEABILI'Iaf AFTER BACrERIAL CHALLENGE Not infrequently, the pulp will demonstrate healing and repair in spite of dentin being continously exposed to thc oral environment. In fact, it appears that dentin which has been bacterially challenged for some time looses its permeability to bacterial elements. We have reported, for example, in an experimental study conducted in both humans and monkeys
99
that continous bacterial provocation of dentin does not necessarily result in progressive inflammatory breakdown of the pulp (11). More often, pulpal healing and repair were encountered 30 days after the initiation of the bacterial provocation. This observation suggests that bacterial irritation of an area of exposed dentin will cause pulpai lesions only of a limited duration and leave little permanent damage (for review see ref. 3). Similarly, under clinical conditions dentin may be covered long term by bacterial plaque after, for example, attrition, abrasion, dental trauma, or root exposure in periodontal therapy. Most often in these situations it seems that the pulp is not seriously affected and will remain vital and functional. The most likely explanation for this phenomenon is that the permeability of the affected dentin has been reduced or blocked. Although reparative dentin may provide protection of the pulp against noxious agents (12), disappearance of inflammatory cell infiltrates was noted before reparative dentin had developed (11). Thus, reparative dentin is most likely not the factor that governs the healing process of the pulp in its response to bacterial challenge. Based on a series of experimental findings, Pashley et at. (13, 14) have proposed that after fresh exposure of dentin a restriction of the tubules is initiated that would reduce or prevent the permeation of particulate matters. They noted that dentin permeability, as measured by fluid filtration and isotope clearance, decreased significantly within hours after dentin was exposed peripherally. Findings in other experiments suggested that precipitation of high molecular weight proteins, such as fibrinogen, was responsible for the observed reduction in dentin permeability (15). In other words the outward flow of dentinal fluids, which follow exposure of dentin, may carry plasma proteins such as fibrinogen from injured capillaries in the pulp, and this could reduce the functional radius of the tubules. If this phenomenon, in fact, is occuring, one may also speculate that antibodies capable of binding antigens that enter the exposed ends could block the tubules further by the buildup of immune complexes. The potential of such a mechanism has been raised by the finding of immunoglobulin depositions in dentin affected by caries (16, 17). As yet, we have an incomplete understanding of the dynamic changes that may take place in dentin after bacterial influences. There is a need to enhance our knowledge of this important problem area in the pulp biology field. P U L P A L I M M U N E D E F E N S E SYSTEMS Substances released from bacteria can affect the host defense in a number of different ways. Except for being directly chemotactic to cells of the inflammatory defense, bacterial substances may also in a more indirect way trigger the host defense by, for example, activation of the complement system. In addition, they may function as antigens and activate various forms of immunne reactions. One must also remember that bacteria can be directly damaging to tissues by the release of various enzymes and metabolites. To what extent this latter mechanism is significant in causing pulpal injury across a dentin barrier is not well understood. The question of whether the pulp is capable of immune defense reactions has not been the subject of much investi-
100
Bergenholtz
Joumal of Endodonbcs
gation. Well over 10 yr ago we demonstrated that antigenic challenge of exposed dentin indeed can trigger immune pathological reactions in the pulp (18). However, it was not until very recently that it was shown that the pulp is equipped with the necessary cellular components for the initial recognition and the subsequent processing of antigens (19, 20). Until then it was assumed that the normal dental pulp was devoid of immunocompctent cells except for macrophages (histiocytes) that frequently can be seen adjacent to blood vessels. Using immunohistochemistry with monoclonal antibodies to a variety ofimmunocompetent cells on frozen and acetonefixed tissue sections of normal human dental pulps, Jontell et al. (19) found, contrary to previous assumptions, that the pulp contains a variety of immune cells. The large majority of cells were peripheral T cells (helper/inducer and cytotoxic/suppressor, Fig. 1), but also cells with the reported capacity for antigen presentation were identified. One of these cells had a dendritic appearance and was located primarily in the odontoblastic layer (Fig. 2). Dendritic cells have been identified also in other tissues for example mucosal and lymphoid tissue. These cells express HLA-DR antigens on their cell surface and are known to be associated with immunosurveillance and antigen presentation. It is not unreasonable to assume that the dendritic cells observed in the pulp have similar functions. The other antigen-presenting cells had features similar to macrophages and were located in the more central portions of the pulp. In a subsequent report we determined the numeric ratio between these cells and dendritic cells with flow cytometry and found that Class I1 antigen activated macrophages are four times as c o m m o n as dendritic cells in the rat incisor (20). The significance of this finding is not known. It is noteworthy that the normal dental pulp does not seem to have B cells (19). The functional role and the interplay of the various immunocompetent cells in the pulp is currently under investigation.
,t
_~"~e
-'-:.,~"~t~
'-~- ,' "~-
o,
f,
I
p
FIG 2. Immunohistochemical demonstration of dendritic cells in the periphery of a human dental pulp. Reprinted with permission from Jontell et al. (19).
CONCLUSION Available data seem to show that the pulp is well adapted to its environment. It is capable of defending itself against
J 9
'e
"
.
-
'
~9 ~P
t~r .~,
99
.~,
FoG1. Immunohistochemical demonstration of T cells in normal human pulp tissue specimen. Reprinted with permission from Jontell et al. (19).
FIG 3. Schematic drawing depicting different defense elements in the normal dental pulp. 1, dendritic cells adjacent to the odontoblastic cell layer; 2, blood vessel with emerging neutrophil; 3, macrophage; 4, T cell; 5, odontoblast precursor cell.
microbial insults in a number of ways. A ,schematic drawing (Fig. 3) depicts dendritic cells that may be associated with functions in immunosurveillance and antigen presentation, blood vessels that bring essential defense cells, macrophages with functions for recognition, and presentation of antigens to T helper cells. Furthermore, there are pulpal stroma cells that on proper signals migrate to sites of injury, differentiate to repairing odontoblasts, and execute dentinal repair. The dental pulp is a fascinating tissue which has attracted the attention of our profession in all times. The amount of data that has accumulated over the years on the biology and the clinical behavior of this tissue is impressive. Yet, there are considerable gaps in our knowledge of the defense and repair mechanisms of the dentin-dental pulp complex that future research will have to address.
Vol. 16, No. 2, February 1990 Dr. Bergenhbltz is affiliated with the Department of Endodontology/Oral DiagnOsis, Faculty o10dontology, Unwersity of Gothenburg, Gothenburg, Sweden. Address requests for reprints to Dr. Gunnar Bergenholtz, Department of Endodontology/OraJ Diagnosis, Faculty of Odontelogy, L~iversity of Gothenburg, Box 330 70, S-400 33 Gothenburg, Sweden.
References 1. Kakehashi S, Stanley HR, Fitzgerald RJ. The effects of surgical exposures of dental pulp in germ free and conventional laboratory rats. Oral Surg 1965;20:340-9. 2. Kakehashi S, Stanley HR, Fitzgerald RJ. The exposed germ free pulp: effects of topical corticostero~d medEat~on and restoration. Oral Surg 1969:27:60-7. 3. Bergenhbltz G. Bacterial leakage around dental restorations--impact on the pulp In: Anusavice KJ, ed. Quality evaluation of dental restorations. Lombard. IL: Quintessence Publishing Co., 1989:243-54. 4. Cox CF, Keall CL. Keall HJ, Ostro E, BergenhoJtz G. Biocompatibility of surface-sealed dental materials against exposed pulps. J. Prosthet Dent 1987;57:1-8. 5. Brannstrom M, Nyborg H. Cavity treatment with a microbicldal fluoride solution: growth of bactena and effect on the pulp. J Prosthet Dent 1973;30:303-10. 6. Lundy T, Stanley HR. Correlation of pulpal histopatbology and c_Jinical symptoms in human teeth subjected to expenmental irritation. Oral Surg 1969;27:187-201. 7. Bergenholtz G. Effect of bactenat products on ~nflammatory reactions in the dental pulp. Stand J Dent Res 1977;85:122-9.
Mechanisms of Pulpal Disease
101
8. Bergenholtz G, Lindhe J Effect of soluble plaque factors on inflammatory reactions in the dental pulp. Scand J Dent Res 1975;83:153-8. 9. Bergenholtz G, Warfvmge J. M~jration of leuko(:ytes in dental pulp in response to plaque bactena Scand J Dent Res 1982;90:354-62. 10. Warfvinge J, Dahlen G, Bergenholtz G, Dental I~JIpresponse to bacterial cell wall material. J Dent Res 1985;64:1046-50. 11. Warfvinge J Bergenholtz G Healing capacity of human and monkey dental pulps fellowing experimentally induced pulpit]s. Ended Dent Traumatol 1986;2:256-62. 12. EI-Kafrawy AH, Mitchell DF. Pulp reactions to open cavities later restored with silicate cement. J Dent Res 1963;42:874-84. 13. Pashley DH, Kepler EE, Williams EC, Okabe A. Progressive decrease in dentine permeability ~ollowmg cavity preparation Arch Oral Biol 1983;28:853-8. 14. Pashley DH, Kepler EE, Williams EC, O'Meara JA. The effect on dentine permeability of time fellow,ng cavity preparation in dogs. Arch. Oral Bioi 1984;29:65-8. 15. Pashley DH, Galloway SE, Steward FP. Dentine permeability: effect of fibrinogen, in vivo. Arch Oral Bio11984;29:725-8. 16. Okamura K, Maeda M, Nishikawa T, Tsutsui M Dentinal response against carious invasion: localization of antibodies in odontoblast~c body and process. J Dent Res 1980;59:1368-73. 17. Ackefman F, Klein JP, Frank RM. Ultrastructural localization of immunoglobulins m carious human dentine. Arch Oral Bio11981 ;26:879-86. 18. Bergenholtz G, Ahlstedt S, IJndhe J. Experimental pulpitls in immunized monkeys. Scand J Dent Res 1977;85:396-406. 19. Jontell M, Gunral M, Bergenholtz G. Immunocompetent ce~ls in normal dental pulp. J Dent Res 1987;66:1149-53. 20. Jontell M, Bergenholtz G, Scheynius A, Ambrose W. Dendritic cells and macrophages expressing Class II antigens m the normal rat incisor pulp. J Dent Res 1988;67:1263-6.
Printed in U.S.A. VOL. 16, NO 2, FEBRUARY1990
Pathogenic Mechanisms in Pulpal Disease Gunnar Bergenholtz, DDS, Odont. Dr.
The unpredictable response of the dental pulp to clinical insults is frequently encountered in the daily practice of dentistry. Even though the pulp often shows remarkable capacity for recovery, painful symptoms and pulp tissue breakdown may follow such clinical insults as caries, dental trauma, or operative dental procedures. In recent years pulp biology research has provided a deeper insight into the basic mechanisms that govern pulpal defense and repair. This communication focuses on dentin permeability to bacterial antigens and how bacterial elements may be processed and dealt with by the dentin-dental pulp complex.
other hand, pulpal tissue healing and hard tissue repair consistently occurred in spite of the fact that the palpal exposures were filled with food debris, hair, and other matter (i). Bacterial influences are also highly significant in the pathogenesis of pulpal inflammatory lesions under dental restorations. Experimental studies in humans and animals carried out over the past 15 yr have shown a strong association between pulpal lesions and marginal leakage of bacteria, while dental restorative materials per se cause little or no irritation of the pulp provided marginal leakage has been effectively prevented (for review see ref. 3). Very recently, Cox et at. (4) added strong support for the concept of bacterial influences being a major factor in the development of puipal lesions following restorative therapy. They investigated in monkeys the direct effect of a variety of common dental materials on the pulpal tissue. Through Class V cavity preparations they exposed the pulp and placed the restorative materials over the exposure site. To prevent marginal leakage, the outer portion of the restoration was removed and substituted with zinc-oxide eugenol cement according to the method designed by Br~innslrdm and Nyborg (5). In control cavities no such surface seal was conducted. Histological findings 3 wk after the initiation of the experiment showed pulp tissue reorganization and hard tissue repair with silicate cement, composite, and zinc phosphate cement restorations. This type of healing was observed only in teeth where a zinc oxide-eugenol cement surface seal had been placed. On the other hand, severe inflammation and necrosis were noted under restorations without a surface seal. In these latter teeth bacteria were often found at the pulp tissue-restoration interface. A large number of investigations carried out during the past 15 to 25 yr implicate bacterial infection as a most important factor in pulpal disease pathogenesis. It is obvious that it is from this basis that the answers to the sometimes erratic behavior of the pulp to clinical injury and painful events should be sought.
The connective tissue of the dental pulp is located in a very special environment. It is surrounded by a tough encasement of hard tissue, i.e. dentin, cementum, and enamel that normally provides strong mechanical support and protection. As long as this hard tissue barrier is intact, the pulp will not be exposed to adverse influences from injurious elements present in the oral environment, and it will under this condition remain in a healthy and functional slate. However, in a number of clinical situations well known to the dentist (Table l), teeth suffer the loss of hard tissue integrity. When the outer enamel or cementum layers are broken through, the potential exists for noxious components in the oral environment to gain access to the pulp and adversely influence the tissue along exposed dentinal tubules. I M P A C T OF T H E ORAL M I C R O B I O T A In the oral cavity a number of elements are present which potentially can be injurious to the pulp. It is now well documented that bacteria and bacterial by-products are associated with most pulpal disease processes and that, for example, food items and components from restorative materials in common use in dentistry today, play relatively insignificant roles. The classical experiments by Kakehashi et al. (I, 2) laid essential groundwork for our current concepts regarding the impact of the oral microbiota in palpal disease and demonstrated in conventional and germ-free rats that bacterial infection is a key factor. After exposure of pulps to the oral environment, they observed palpal necrosis and periapical abscesses in conventional rats. In the germ-free rats, on the
PERMEABILITY OF DENTIN TO BACTERIAL ANTIGENS A critical question is whether a walt of dentin separating the pulp from the oral environment can provide protection of the pulp against bacterial influences. Experiments have demonstrated that although dentinal tubules can be invaded by oral microorganisms after bacterial plaque accumulation, bacterial penetration of noncarious dentin to the pulp is a rare finding even after long-term exposure of dentin to the 98
Vol. 16, No. 2, February 1990
Mechanisms of Pulpal Oiseese
TABLE 1. Major etiological factors of pulpal disease Microbial Caries Periodontal disease
Traumatic
latrogenic
Concussion/luxation injuries Crown/root fractures
Trauma from operative procedures Marginal leakage Dental material toxicity
oral microflora (6). However, during clinical procedures one can facilitate bacterial invasion of the pulp by eliminating the smear layer and opening up the tubular orifices by acid etch procedures before restoration. If dentinal tubules have not been properly blocked or covered by a base material or liner and if the subsequent restoration has a poor marginal adaptation, bacteria may gain direct access to the pulp. Even though oral microorganisms, in general, have limited capacities to invade the pulp along dentin, it is clear from a number of experimental studies that dentin is not an effective barrier against the diffusion of bacterial components. In a series of experimental studies carried out in our laboratory (7-11 ), we have employed an experimental model that made use of Class V cavities preparations in teeth of monkeys or humans. These cavities were used to test the influence on the pulp of bacterial substances of various types after their topical application to fresh preparations of dentin. These experiments have demonstrated that the dentin-dental pulp complex responds rapidly to bacterial challenges. Findings also suggest that a thin wall ofcoronal dentin is unable to prevent bacterial substances, including high molecular weight complexes of bacterial cell walls, from adversely affecting the underlying pulp. Even the presence of a smear layer does not seem to prevent the diffusion of bacterial substances along the dentinal tubules, since in none of our experiments were attempts made to remove this debris by EDTA or acids. Based on these findings it is reasonable to conclude that fresh exposures of dentin are highly permeable to bacterial elements present in saliva or released from bacterial plaques. One must remember, however, that in none of our experiments have we proven that bacterial components actually are being transported through dentin to the pulp, where the inflammatory responses are induced. In other words, it may be that bacterial elements do not penetrate at all or just enter the dentin a short distance. Thus, the potential exists that the initial reactions of the host defense including the migration of polymorphonuclear neutrophils are initiated through the activation of some form of host defense mechanism present within the dentinal fluids. This implies that inflammatory lesions, developing in the pulp in response to bacterial irritation of exposed dentin, may be initiated either by the diftusion of bacterial elements and/or the activation of signal substances released from the dentinal fluids. CHANGES IN D E N T I N PERMEABILI'Iaf AFTER BACrERIAL CHALLENGE Not infrequently, the pulp will demonstrate healing and repair in spite of dentin being continously exposed to thc oral environment. In fact, it appears that dentin which has been bacterially challenged for some time looses its permeability to bacterial elements. We have reported, for example, in an experimental study conducted in both humans and monkeys
99
that continous bacterial provocation of dentin does not necessarily result in progressive inflammatory breakdown of the pulp (11). More often, pulpal healing and repair were encountered 30 days after the initiation of the bacterial provocation. This observation suggests that bacterial irritation of an area of exposed dentin will cause pulpai lesions only of a limited duration and leave little permanent damage (for review see ref. 3). Similarly, under clinical conditions dentin may be covered long term by bacterial plaque after, for example, attrition, abrasion, dental trauma, or root exposure in periodontal therapy. Most often in these situations it seems that the pulp is not seriously affected and will remain vital and functional. The most likely explanation for this phenomenon is that the permeability of the affected dentin has been reduced or blocked. Although reparative dentin may provide protection of the pulp against noxious agents (12), disappearance of inflammatory cell infiltrates was noted before reparative dentin had developed (11). Thus, reparative dentin is most likely not the factor that governs the healing process of the pulp in its response to bacterial challenge. Based on a series of experimental findings, Pashley et at. (13, 14) have proposed that after fresh exposure of dentin a restriction of the tubules is initiated that would reduce or prevent the permeation of particulate matters. They noted that dentin permeability, as measured by fluid filtration and isotope clearance, decreased significantly within hours after dentin was exposed peripherally. Findings in other experiments suggested that precipitation of high molecular weight proteins, such as fibrinogen, was responsible for the observed reduction in dentin permeability (15). In other words the outward flow of dentinal fluids, which follow exposure of dentin, may carry plasma proteins such as fibrinogen from injured capillaries in the pulp, and this could reduce the functional radius of the tubules. If this phenomenon, in fact, is occuring, one may also speculate that antibodies capable of binding antigens that enter the exposed ends could block the tubules further by the buildup of immune complexes. The potential of such a mechanism has been raised by the finding of immunoglobulin depositions in dentin affected by caries (16, 17). As yet, we have an incomplete understanding of the dynamic changes that may take place in dentin after bacterial influences. There is a need to enhance our knowledge of this important problem area in the pulp biology field. P U L P A L I M M U N E D E F E N S E SYSTEMS Substances released from bacteria can affect the host defense in a number of different ways. Except for being directly chemotactic to cells of the inflammatory defense, bacterial substances may also in a more indirect way trigger the host defense by, for example, activation of the complement system. In addition, they may function as antigens and activate various forms of immunne reactions. One must also remember that bacteria can be directly damaging to tissues by the release of various enzymes and metabolites. To what extent this latter mechanism is significant in causing pulpal injury across a dentin barrier is not well understood. The question of whether the pulp is capable of immune defense reactions has not been the subject of much investi-
100
Bergenholtz
Joumal of Endodonbcs
gation. Well over 10 yr ago we demonstrated that antigenic challenge of exposed dentin indeed can trigger immune pathological reactions in the pulp (18). However, it was not until very recently that it was shown that the pulp is equipped with the necessary cellular components for the initial recognition and the subsequent processing of antigens (19, 20). Until then it was assumed that the normal dental pulp was devoid of immunocompctent cells except for macrophages (histiocytes) that frequently can be seen adjacent to blood vessels. Using immunohistochemistry with monoclonal antibodies to a variety ofimmunocompetent cells on frozen and acetonefixed tissue sections of normal human dental pulps, Jontell et al. (19) found, contrary to previous assumptions, that the pulp contains a variety of immune cells. The large majority of cells were peripheral T cells (helper/inducer and cytotoxic/suppressor, Fig. 1), but also cells with the reported capacity for antigen presentation were identified. One of these cells had a dendritic appearance and was located primarily in the odontoblastic layer (Fig. 2). Dendritic cells have been identified also in other tissues for example mucosal and lymphoid tissue. These cells express HLA-DR antigens on their cell surface and are known to be associated with immunosurveillance and antigen presentation. It is not unreasonable to assume that the dendritic cells observed in the pulp have similar functions. The other antigen-presenting cells had features similar to macrophages and were located in the more central portions of the pulp. In a subsequent report we determined the numeric ratio between these cells and dendritic cells with flow cytometry and found that Class I1 antigen activated macrophages are four times as c o m m o n as dendritic cells in the rat incisor (20). The significance of this finding is not known. It is noteworthy that the normal dental pulp does not seem to have B cells (19). The functional role and the interplay of the various immunocompetent cells in the pulp is currently under investigation.
,t
_~"~e
-'-:.,~"~t~
'-~- ,' "~-
o,
f,
I
p
FIG 2. Immunohistochemical demonstration of dendritic cells in the periphery of a human dental pulp. Reprinted with permission from Jontell et al. (19).
CONCLUSION Available data seem to show that the pulp is well adapted to its environment. It is capable of defending itself against
J 9
'e
"
.
-
'
~9 ~P
t~r .~,
99
.~,
FoG1. Immunohistochemical demonstration of T cells in normal human pulp tissue specimen. Reprinted with permission from Jontell et al. (19).
FIG 3. Schematic drawing depicting different defense elements in the normal dental pulp. 1, dendritic cells adjacent to the odontoblastic cell layer; 2, blood vessel with emerging neutrophil; 3, macrophage; 4, T cell; 5, odontoblast precursor cell.
microbial insults in a number of ways. A ,schematic drawing (Fig. 3) depicts dendritic cells that may be associated with functions in immunosurveillance and antigen presentation, blood vessels that bring essential defense cells, macrophages with functions for recognition, and presentation of antigens to T helper cells. Furthermore, there are pulpal stroma cells that on proper signals migrate to sites of injury, differentiate to repairing odontoblasts, and execute dentinal repair. The dental pulp is a fascinating tissue which has attracted the attention of our profession in all times. The amount of data that has accumulated over the years on the biology and the clinical behavior of this tissue is impressive. Yet, there are considerable gaps in our knowledge of the defense and repair mechanisms of the dentin-dental pulp complex that future research will have to address.
Vol. 16, No. 2, February 1990 Dr. Bergenhbltz is affiliated with the Department of Endodontology/Oral DiagnOsis, Faculty o10dontology, Unwersity of Gothenburg, Gothenburg, Sweden. Address requests for reprints to Dr. Gunnar Bergenholtz, Department of Endodontology/OraJ Diagnosis, Faculty of Odontelogy, L~iversity of Gothenburg, Box 330 70, S-400 33 Gothenburg, Sweden.
References 1. Kakehashi S, Stanley HR, Fitzgerald RJ. The effects of surgical exposures of dental pulp in germ free and conventional laboratory rats. Oral Surg 1965;20:340-9. 2. Kakehashi S, Stanley HR, Fitzgerald RJ. The exposed germ free pulp: effects of topical corticostero~d medEat~on and restoration. Oral Surg 1969:27:60-7. 3. Bergenhbltz G. Bacterial leakage around dental restorations--impact on the pulp In: Anusavice KJ, ed. Quality evaluation of dental restorations. Lombard. IL: Quintessence Publishing Co., 1989:243-54. 4. Cox CF, Keall CL. Keall HJ, Ostro E, BergenhoJtz G. Biocompatibility of surface-sealed dental materials against exposed pulps. J. Prosthet Dent 1987;57:1-8. 5. Brannstrom M, Nyborg H. Cavity treatment with a microbicldal fluoride solution: growth of bactena and effect on the pulp. J Prosthet Dent 1973;30:303-10. 6. Lundy T, Stanley HR. Correlation of pulpal histopatbology and c_Jinical symptoms in human teeth subjected to expenmental irritation. Oral Surg 1969;27:187-201. 7. Bergenholtz G. Effect of bactenat products on ~nflammatory reactions in the dental pulp. Stand J Dent Res 1977;85:122-9.
Mechanisms of Pulpal Disease
101
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