Hypoxia reoxygenation-induced injury of cultured pulmonary microvessel endothelial cells.
Polymorphonuclear leukocyte (PMN) sequestration within the pulmonary microvasculature is known to occur in association with ischemia/reoxygenation (I/R). This sequestration is dependent on eicosanoids and reactive oxygen species. PMN sequestration within the lungs suggests that pulmonary microvascular endothelial cells (MECs) may in part regulate the I/R response. Simulating I/R, we examined the effect of hypoxia/reoxygenation (H/R) on pulmonary MECs in vitro, with and without PMNs. Significant cellular injury, assessed by 51Cr release, occurred upon reoxygenation of MECs (P < .01). Addition of PMNs to the H/R-injured monolayers did not increase MEC injury. Reoxygenation of MECs also resulted in increased thromboxane (Tx) B2 production compared to controls (P < .01). Inhibition of Tx secretion by aspirin reduced H/R-induced PMN adhesion to MECs (P < .01). Furthermore, H/R-induced increases in PMN-MEC adhesion were prevented by allopurinol and superoxide dismutase (P < .01). These data suggest that the pulmonary response to H/R is mediated by MEC generation of reactive oxygen radical species and Tx, which promotes increased PMN adhesion.
Microvascular Research Laboratory, Boston University, Massachusetts 02215.
M E
ME
Wiles
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Hechtman
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Morel
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Shepro
D000199:Actins / Q000032:analysis; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D002860:Chromium Radioisotopes; D003599:Cytoskeleton / Q000737:chemistry / Q000648:ultrastructure; D003907:Dexamethasone / Q000494:pharmacology; D015777:Eicosanoids / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology*; D007975:Leukotriene B4 / Q000378:metabolism; D008168:Lung / Q000098:blood supply*; D009637:Masoprocol / Q000494:pharmacology; D008833:Microcirculation / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D009504:Neutrophils / Q000166:cytology / Q000502:physiology; D011863:Radioimmunoassay; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000503:physiopathology*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013929:Thromboxane B2 / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
D000199:Actins; D002860:Chromium Radioisotopes; D015777:Eicosanoids; D017382:Reactive Oxygen Species; D007975:Leukotriene B4; D013929:Thromboxane B2; D000493:Allopurinol; D009637:Masoprocol; D003907:Dexamethasone; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase