Berlyne GM (ed): The Kidney Today. Selected Topics in Renal Science. Contrib Nephrol. Basel, Karger, 1992, vol 100, pp 15-24
Phagocytic Function in the U fernic Patient S. Ringoir, R . Vanholder
Phagocytosis is the process whereby certain cells ingest foreign material, and enclose it within a cytoplasmatic vacuole named phagosome, which is subsequently destroyed. The role of phagocytosis in the immune response was underestimated for a long period of time. The importance of phagocytosis in the host defense against infection and cancer recently became more and more apparent, however. The uremic patient displays, as known, an enhanced susceptibility to infection as well as an increased incidence of cancer. Phagocytic cells can be subdivided into polymorphonUclear granulocytes, monocytes, eosinophilic granulocytes, and macrophages. Whereas monocytes only circulate in the blood during a short period of time, they remain present for several consecutive months when they reside in the tissues: they then are called macrophages. Macrophages can be found in the liver (Kupffer cells), in the spleen, in the brain (glia cells), the lungs, the glomeruli (mesangial cells), the serosa, and the lymph nodes. Phagocytes not only have the capacity to kill and destroy bacteria, but they also produce so-called cytokines that have the ability to activate other cells of the immune system such as T and B l ymphocytes, or that may induce general reactions. Interleukin-l (IL-l), produced by macrophages, provokes fever by the stimulation of the fever center. IL-6 is also produced. Tumor necrosis factor (TNF) provokes tumor necrosis, in addition to a whole series of other catabolic side effects. The macrophages also cause antigen processing in favor of the lymphocytic system. During phagocytosis, glucose is metabolized via the hexose monophosphate pathway, which delivers the necessary energy for the production
Downloaded by: Université René Descartes Paris 5 193.51.85.197 - 3/15/2018 2:06:51 PM
Division of Nephrology, Department of Internal Medicine, University Hospital, Ghent, Belgium
Ringoir/Vanholder
16
of free oxygen radicals, H202 and other compounds, that will provoke lysis of phagocytosed material. This process is called respiratory burst. The modern methodology to investigate phagocytic function essentially consists of: (1) The follow-up of respiratory burst during phagocytosis by estimation of glucose metabolization after administration oflabeled glucose and measurement of produced CO 2• Ribose-5-phosphate is indeed transformed to CO 2 in a series of consecutive steps. (2) During the chemical reaction of the respiratory burst, light is produced. This chemiluminescence can be measured in a Lumetron. In uremia one should take into account the possibility that the registration of chemiluminescence would be disturbed by the presence of uremic toxins, that act as scavengers of free radicals. (3) Follow-up ofIL-l, IL-6 or TNF production. For the investigations in our unit, we studied the glucose metabolization and production of C02 in the resting state and after stimulation with latex, zymosan or Staphylococcus aureus. These tests were performed on 50 III of whole blood [2, 3]. There might be a slight bias in the results obtained with whole blood because red blood cells also have a glucose metabolism, but this bias exists only in the resting state and not after challenge, as erythrocytes do not display any phagocytosis.
Evaluation of Phagocytosis in Uremia The following conditions of the uremic state were evaluated: (1) progressive chronic renal failure; (2) first weeks of hemodialysis treatment; (3) intradialytic evolution; (4) evolution during maintenance haemodialysis treatment; (5) continuous ambulatory peritoneal dialysis (CAPO) and renal transplantation, and (6) changes after stimulation of phagocytosis.
Progressive Chronic Renal Failure In a transversal study of an outpatient population of patients with increasing degree of renal failure, it appears that phagocytosis is only modified at a serum creatinine of more than 6 mg/dl, and even more with
Downloaded by: Université René Descartes Paris 5 193.51.85.197 - 3/15/2018 2:06:51 PM
Normal Individuals Normal individuals were first investigated as a control series. We consider as Lllatex, Ll zymosan or Ll S. aureus the increase after stimulation of radioactive disintegrations per minute (dpm), compared to the resting state.
17
Phagocytic Function in the Uremic Patient
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Fig. 1. Transversal evaluation of the glycolytic response towards latex and zymosan in an outpatient population (n = 119), with groups with different serum creatinine. The glycolytic response is only significantly modified from a serum creatinine about 6 mg/dl on. * p < 0.05; ** p < 0.01 vs. creatinine ::s 1.3 mg/dl.
Hemodialysis Patients In a large group of hemodialysis patients, both L1latex and L1 zymosan are considerably suppressed (fig. 3). Remarkably enough, phagocytic function decreases still further during the first weeks of hemodialysis treat-
Downloaded by: Université René Descartes Paris 5 193.51.85.197 - 3/15/2018 2:06:51 PM
serum creatinine above 9 mgldl (fig. 1). This is the period immediately before the start of renal replacement therapy. At a decrease of renal function as indicated by creatinine clearance, from 15 to 5 ml/min, in a prospective study, over a 5-month period, phagocytic function equally decreases significantly (fig. 2) [7].
Ringoir/V anholder
18
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C1l .
Phagocytic Function in the U fernic Patient S. Ringoir, R . Vanholder
Phagocytosis is the process whereby certain cells ingest foreign material, and enclose it within a cytoplasmatic vacuole named phagosome, which is subsequently destroyed. The role of phagocytosis in the immune response was underestimated for a long period of time. The importance of phagocytosis in the host defense against infection and cancer recently became more and more apparent, however. The uremic patient displays, as known, an enhanced susceptibility to infection as well as an increased incidence of cancer. Phagocytic cells can be subdivided into polymorphonUclear granulocytes, monocytes, eosinophilic granulocytes, and macrophages. Whereas monocytes only circulate in the blood during a short period of time, they remain present for several consecutive months when they reside in the tissues: they then are called macrophages. Macrophages can be found in the liver (Kupffer cells), in the spleen, in the brain (glia cells), the lungs, the glomeruli (mesangial cells), the serosa, and the lymph nodes. Phagocytes not only have the capacity to kill and destroy bacteria, but they also produce so-called cytokines that have the ability to activate other cells of the immune system such as T and B l ymphocytes, or that may induce general reactions. Interleukin-l (IL-l), produced by macrophages, provokes fever by the stimulation of the fever center. IL-6 is also produced. Tumor necrosis factor (TNF) provokes tumor necrosis, in addition to a whole series of other catabolic side effects. The macrophages also cause antigen processing in favor of the lymphocytic system. During phagocytosis, glucose is metabolized via the hexose monophosphate pathway, which delivers the necessary energy for the production
Downloaded by: Université René Descartes Paris 5 193.51.85.197 - 3/15/2018 2:06:51 PM
Division of Nephrology, Department of Internal Medicine, University Hospital, Ghent, Belgium
Ringoir/Vanholder
16
of free oxygen radicals, H202 and other compounds, that will provoke lysis of phagocytosed material. This process is called respiratory burst. The modern methodology to investigate phagocytic function essentially consists of: (1) The follow-up of respiratory burst during phagocytosis by estimation of glucose metabolization after administration oflabeled glucose and measurement of produced CO 2• Ribose-5-phosphate is indeed transformed to CO 2 in a series of consecutive steps. (2) During the chemical reaction of the respiratory burst, light is produced. This chemiluminescence can be measured in a Lumetron. In uremia one should take into account the possibility that the registration of chemiluminescence would be disturbed by the presence of uremic toxins, that act as scavengers of free radicals. (3) Follow-up ofIL-l, IL-6 or TNF production. For the investigations in our unit, we studied the glucose metabolization and production of C02 in the resting state and after stimulation with latex, zymosan or Staphylococcus aureus. These tests were performed on 50 III of whole blood [2, 3]. There might be a slight bias in the results obtained with whole blood because red blood cells also have a glucose metabolism, but this bias exists only in the resting state and not after challenge, as erythrocytes do not display any phagocytosis.
Evaluation of Phagocytosis in Uremia The following conditions of the uremic state were evaluated: (1) progressive chronic renal failure; (2) first weeks of hemodialysis treatment; (3) intradialytic evolution; (4) evolution during maintenance haemodialysis treatment; (5) continuous ambulatory peritoneal dialysis (CAPO) and renal transplantation, and (6) changes after stimulation of phagocytosis.
Progressive Chronic Renal Failure In a transversal study of an outpatient population of patients with increasing degree of renal failure, it appears that phagocytosis is only modified at a serum creatinine of more than 6 mg/dl, and even more with
Downloaded by: Université René Descartes Paris 5 193.51.85.197 - 3/15/2018 2:06:51 PM
Normal Individuals Normal individuals were first investigated as a control series. We consider as Lllatex, Ll zymosan or Ll S. aureus the increase after stimulation of radioactive disintegrations per minute (dpm), compared to the resting state.
17
Phagocytic Function in the Uremic Patient
0> CIl
.c
D-
150
'b
E
D-
* **
100
"0
X
2
.!!l CIl
.c
50
400
D-
'b
*
E
D-
"0
C CIl UJ
0
**
200
E >N 9
Serum creallnlne, mgl 100 ml
Fig. 1. Transversal evaluation of the glycolytic response towards latex and zymosan in an outpatient population (n = 119), with groups with different serum creatinine. The glycolytic response is only significantly modified from a serum creatinine about 6 mg/dl on. * p < 0.05; ** p < 0.01 vs. creatinine ::s 1.3 mg/dl.
Hemodialysis Patients In a large group of hemodialysis patients, both L1latex and L1 zymosan are considerably suppressed (fig. 3). Remarkably enough, phagocytic function decreases still further during the first weeks of hemodialysis treat-
Downloaded by: Université René Descartes Paris 5 193.51.85.197 - 3/15/2018 2:06:51 PM
serum creatinine above 9 mgldl (fig. 1). This is the period immediately before the start of renal replacement therapy. At a decrease of renal function as indicated by creatinine clearance, from 15 to 5 ml/min, in a prospective study, over a 5-month period, phagocytic function equally decreases significantly (fig. 2) [7].
Ringoir/V anholder
18
400 0,
ci>
C1l .
