Hypotheses regarding the role of pericytes in regulating movement of fluid, nutrients, and hormones across the microcirculatory endothelial barrier.
A decade ago, we initiated studies to define relationship(s) between products of 5-lipoxygenase-mediated arachidonic acid metabolism and altered microvascular permeability. Patients with permeability (nonhydrostatic) pulmonary edema (adult respiratory distress syndrome) and intact animal models of permeability edema, produced with agents that required neutrophils (phorbol myristate acetate) and those that did not (ethchlorvynol), invariably revealed the presence of leukotrienes; in contrast, leukotrienes were not detected in cases of hydrostatic pulmonary edema. In isolated perfused canine lung, we identified increases in microvascular permeability coefficients in response to the injurious agent. Permeability coefficients were not increased when injurious agents were given in the presence of 5-lipoxygenase inhibitors. To define further the relationships between leukotriene generation and edema formation, we postulated 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 enzyme; however, when cocultured with neutrophils, which possess 5-lipoxygenase but cannot synthesize sulfidopeptide leukotrienes because of their lack of glutathione S-transferase, sulfidopeptide leukotriene synthesis ensued. 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 communication, we propose that pericytes control the movement of fluid, solutes, hormones, and small and large molecules across the microvascular endothelium.
Department of Internal Medicine, Saint Louis University School of Medicine, Missouri 63104, USA.
A J
AJ
Lonigro
L
L
McMurdo
A H
AH
Stephenson
R S
RS
Sprague
N L
NL
Weintraub
D000818:Animals; D001692:Biological Transport; D002196:Capillaries / Q000166:cytology*; D002199:Capillary Permeability; D002417:Cattle; D004049:Diethylcarbamazine / Q000494:pharmacology; D004285:Dogs; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D015289:Leukotrienes / Q000502:physiology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D012128:Respiratory Distress Syndrome / Q000503:physiopathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014882:Water-Electrolyte Balance
D007328:Insulin; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D013755:Tetradecanoylphorbol Acetate; D004049:Diethylcarbamazine