Hypoxia induces endothelial cells to increase their adherence for neutrophils: role of PAF.
We investigated the interactions of polymorphonuclear neutrophils (PMN) and endothelial cells in myocardial ischemia using a hypoxia model. We exposed porcine aortic (PAEC) and porcine coronary microvessel (PCMEC) endothelial cells to 2% O2 for 2 h (PO2 = 53 mmHg) and measured the adherence of unstimulated neutrophils (PMN) to both control and hypoxia-conditioned endothelial cell monolayers. Hypoxia conditioning increased PMN adherence to PAEC and PCMEC by 51 and 101%, respectively, above control levels. The increase in PMN adhesion to PAEC was associated with a threefold increase in endothelial cell-associated platelet-activating factor (PAF) compared with control PAEC. The conditioned media from PAEC exposed to hypoxia also contained sixfold more PAF than control conditioned media, and it activated PMN to become adherent to untreated PAEC. The hypoxia-induced PAEC adhesion response was inhibited by preincubating PMN with the specific PAF receptor antagonist, L-659,989. We conclude that PAF is produced by cultured endothelial cells in response to hypoxia and that PAF generation is chiefly responsible for the increased adherence properties of hypoxia-conditioned endothelial cells. This response may play a major role in regulating PMN margination during myocardial ischemia.
Milhoan
K A
KA
Department of Pathology, University of California, San Diego, La Jolla 92093.
Lane
T A
TA
Bloor
C M
CM
D000818:Animals; D001011:Aorta / Q000473:pathology / Q000503:physiopathology; D002448:Cell Adhesion / Q000187:drug effects; D003331:Coronary Vessels / Q000473:pathology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010100:Oxygen / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000378:metabolism / Q000502:physiology*; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins / Q000473:pathology / Q000503:physiopathology
D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha; D066246:ErbB Receptors; D010100:Oxygen