Elcosanoids PG~ and PGF2a Enhance the Attachment of Rabbit Tracheal Epithelial cells to 'a. Collagen Substrate* I. A. Mardini, M.D., Ph.D.; S. Zhou, M.D.; K. Blank, Ph.D.; and S. G. Kelsen, M.D., F.C.C.R

Inflammation of the airways is associated with release of inflammatory mediators into the airway lumen and denudation of the epithelial lining. Prostaglandins are produced in copious amounts in epithelial cells in response to stimulation by peptide inHammatory mediators. Prostaglandins stimulate epithelial proliferation in other epithelial cell systems. This study was designed to examine the role PGE! or PGF.. may play in enhancing epithelial cell proliferation and/or attachment to a collagen substrate in vitro. Tracheal epithelial cells from adult rabbits (n =5) were harvested by overnight exposure to pronase and plated (1.5 x lOS/em!) on collagen type I-coated cell culture dishes. Cells were incubated at 3~C in serum-free Ham's Fl2 medium supplemented with epidermal growth factor, insulin, transferrin, hydrocortisone, penicillin, and gentamicin with the addition ofPGE 2 , PGF.., both or neither. The presence of PGE 2 (0.15 f.LM) or PGF2a (0.1 f.LM) increased the number of cells attached to the collagen substrate 4, 8, and 24 h after plating, but had no effect on the total number of cells recovered within the first 24 h. The combination of PGE 2 and PGF.. was no more potent than PGE! alone. PGE I and PFG2a significantly increased the number of both attached anel total cells recovered at every time point in culture from 2 to 9 days. However, the fold increase in cell number from day 1 through day 9 was similar in prostaglandin-treated and control dishes. Tritiated thymidine incorporation in cells incubated with or without PGE! was not significantly different. The effect of PGE 2 on attachment was further examined by plating epithelial cells on dishes coated with varying amounts of collagen. After 4 h, cells exposed to PGE 2 attached in higher numbers in all the wells coated with collagen type 1 (0.1 to 100 f.Lglwell), while PGE! had no effect on attachment of epithelial cells to plastic (no collagen). These results suggest that PGE 2 and PGF.. promote attachment of tracheobronchial epithelial cells to a collagen substrate, but have little or no effect on cell proliferation. We speculate that eicosanoids secreted by airway epithelial cells may promote repair ofdenuded aiJway mucosa by stimulating tracheal epithelial cell attachment to the basement membrane. ·From the Departments of Medicine (Pulmonary Section), Physiology and Microbiolo~ School of Medicine, Temple University, Philadelphia. This study was support in part by Cystic Fibrosis Foundation 1095 0-1 and NIH HL 45964-01.

Functional Assessment of Viability of Epithelial cells* Comparison of Viability and Mediator Release In Healthy SUbjects and Asthmatics A CampbeU, Ph.D.; A. Vignola, M.D.; ~ Chane:., M.D.; I. Couret, M.D.; F. B. Michel, M.D., F.C.C.~; J Bousquet, M.D. and ~ H. Godard, M.D.


ronchial asthma is characterized by a chronic desquamative bronchitis with eosinophilia. I Although other cell types infiltrate the bronchi, epithelial desquamation seems to be an important feature of asthma and was described as early as the turn of the century in patients who had died from asthma. I The shedding of ciliated epithelial cells from basal cells appears to he, at least partly, due to eosinophil granule proteins. I When the ciliated epithelial cells are still present, the epithelium has a "fragile" appearance,3 the ciliated cells appearing swollen, vacuolized, and often show loss of cilia. 4,5 However, partial epithelial shedding can be observed in normal nonsmoking subjects,5,6 and the importance of epithelial desquamation observed in biopsy specimens obtained by fiberoptic bronchoscopy needs further evaluation. The role of bronchial epithelium in asthma is unclear, although it is known that in normal subjects, stimulated epithelial cells can release 15-hydroxyeicosatetranoic acid (I5-HETE)7.8 and small amounts of prostaglandins E2 and F Ia .8,9 Following a period in culture, epithelial cells appear to be capable of producing increased levels of PGE2 ,10 a mediator which acts as a bronchodilator in most subjects. Fibronectin is a large glycoprotein present in the extracellular matrix with a large number of binding sites for both cells and for other molecules. It is involved in epithelial cell adhesion and spreading and has been shown to increase epithelial cell regeneration, suggesting an important role for fibronectin in the repair mechanisms of epithelial cell injury.U,12 Studies using bovine bronchi have shown that these epithelial cells can release a chemotactic factor for airways epithelial cells and that this factor is likely to he 6bronectin. 13 There has been an increasing amount of evidence that human airways epithelial cells may be capable of playing a role in the presentation of antigen to T-Iymphocytes, and one of the features of cells capable of carrying out this function is the expression of class II MHe molecules, such as HLA-DR, on their surface. We also investigated whether there was a difference in the expression of class II major histocompatibility molecules in asthma. METHODS

Healthy subjects (0 = 13, mean age = 46 ± 5 years) and asthmatic subjects (n = 13, mean age = 46 ± 7 years) were studied. None of the subjects smoked, and asthmatics were treated only with P-2 agonists. Airways epithelial cells were obtained by brushing of the airways dUring 6beroptic bronchosco~ Cells were examined after *From the Hospital Aiguelongue, Montpellier, France. This study was sup~rted by CERID Pierre Fabre, RamoovilleSt Agne, France, and by grant 88MR4 from the Fonds special du lutte contre les maladies respiratoires, and CNR, Palermo, Italy. CHEST I 101 I 3 I MARCH, 1992 I Supplement


Eicosanoids PGF2 and PGE2 alpha enhance the attachment of rabbit tracheal epithelial cells to a collagen substrate.

Elcosanoids PG~ and PGF2a Enhance the Attachment of Rabbit Tracheal Epithelial cells to 'a. Collagen Substrate* I. A. Mardini, M.D., Ph.D.; S. Zhou, M...
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