Leukotrienes C4 and D4 stimulate human endothelial cells to synthesize platelet-activating factor and bind neutrophils.
AUTOR(ES)
McIntyre, T M
RESUMO
Human endothelial cells in culture produced platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) when stimulated with leukotriene C4 or D4 (LTC4 or LTD4). Other arachidonate metabolites did not induce the synthesis of PAF. Accumulation of PAF was a prolonged response with maximal accumulation after 10-20 min of stimulation. Half of this amount remained after 90 min of stimulation. The PAF synthesized by endothelial cells remained associated with these cells. LTC4 and LTD4 also induced the adherence of human neutrophils (polymorphonuclear leukocytes; PMNs) to the endothelial cell monolayer. Adhesion was an endothelial cell-mediated process because PMNs adhered to monolayers that had been stimulated and washed prior to PMN addition, and neither LTC4 nor LTD4 stimulated PMNs in the absence of endothelial cells. The time course of PMN adhesion paralleled that of PAF accumulation by endothelial cells, and exogenously added PAF induced adherence. PMNs specifically desensitized to PAF showed only 39% of the agonist-stimulated adherence of control PMNs. We conclude that the PAF synthesized and retained by LTC4- or LTD4-stimulated endothelial cells may induce the adherence of previously unstimulated PMNs. This process may be relevant to inflammation, thrombosis, and mechanisms of vascular injury, including atherosclerosis.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=323260Documentos Relacionados
- Binding and metabolism of platelet-activating factor by human neutrophils.
- Cultured endothelial cells synthesize both platelet-activating factor and prostacyclin in response to histamine, bradykinin, and adenosine triphosphate.
- Interleukin 1 stimulates platelet-activating factor production in cultured human endothelial cells.
- Release of leukotriene C4 by isolated, perfused rat small intestine in response to platelet-activating factor.
- Rickettsial stimulation of endothelial platelet-activating factor synthesis.