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DIABETES, VOLUME 45, SUPPLEMETN 1, JANUARY 1996, PAGES S38-S43

Hypotheses Regarding the Role of Pericytes in Regulating Movement of Fluid, Nutrients, and Hormones Across the Microcirculatory Endothelial Barrier

Andrew J. Lonigro, Lorraine McMurdo, Alan H. Stephenson, Randy S. Sprague, and
Neal L. Weintraub

A decade ago, we initiated studies to define relation-ship(s) between products of 5-lipoxygenase-mediated arachidonic acid metabolism and altered microvascular permeability. Patients with permeability (nonhydro-static) pulmonary edema (adult respiratory distress syn-drome) and intact animal models of permeability edema, produced with agents that required neutrophils (phorbol myristate acetate) and those that did not (ethchlorvy-nol), invariably revealed the presence of leukotrienes; in contrast, leukotrienes were not detected in cases of hydrostatic pulmonary edema. In isolated perfused ca-nine lung, we identified increases in microvascular per-meability coefficients in response to the injurious agent. Permeability coefficients were not increased when injuri-ous agents were given in the presence of 5-lipoxygenase inhibitors. To define further the relationships between leukotriene generation and edema formation, we postu-lated that leukotrienes effected contraction of capillary pericytes, thereby increasing pore size of endothelial intercellular junctions and enhancing movement across the microvascular barrier. We isolated pericytes from bovine retinas, identified them morphologically and by staining characteristics, and, in preliminary experiments, found that they do not possess the 5-lipoxygenase en-zyme; however, when cocultured with neutrophils, which possess 5-lipoxygenase but cannot synthesize sulfidopep-tide leukotrienes because of their lack of glutathione S-transferase, sulfidopeptide leukotriene synthesis en-sued. In view of the anatomic position of pericytes, evidence that they participate in endothelial transport, their ability to contract, and evidence of cell-to-cell com-munication, we propose that pericytes control the move-ment of fluid, solutes, hormones, and small and large molecules across the microvascular endothelium. Diabetes 45 (Suppl. 1):S38-S43, 1996

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