Rabbit leukocytes activated by C5a des Arg and N-formyl-methionyl-leucyl-phenylalanine promote endothelial prostacyclin production. Evidence for a role of hydrogen peroxide.
Prostacyclin (PGI2) production by an intact endothelial cell layer on the surface of isolated rabbit aortas was investigated in the presence of chemoattractants (C5a des Arg, FMLP, LTB4, PAF) and autologous blood leukocytes. Leukocytes themselves did not produce detectable amounts of PGI2, nor did they alter basal endothelial PGI2 formation. In the absence of leukocytes, C5a des Arg (but not FMLP, LTB4 or PAF) produced a direct and dose-dependent stimulation of PGI2 release from endothelial cells. This effect was greatly enhanced when C5a des Arg and leukocytes were incubated together on the endothelium. Similar results were obtained on co-incubation of endothelium and leukocytes with FMLP and to a lesser extent with LTB4 and PAF. Experiments with superoxide dismutase and catalase suggest that release of H2O2 may partly explain the stimulatory activity of leukocytes in the presence of chemoattractants. The effect of aspirin treatment of the endothelial cells in enhancing leukocyte adherence induced by C5a des Arg suggests that local PGI2 production by vascular endothelium may provide a natural defence mechanism by attenuating cell-cell interactions.
Rampart
M
M
MRC Clinical Research Centre, Harrow, Middlesex, United Kingdom.
Jose
P J
PJ
Williams
T J
TJ
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D015937:Complement C5a, des-Arginine / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D007975:Leukotriene B4 / Q000494:pharmacology; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D011817:Rabbits
D015937:Complement C5a, des-Arginine; D007975:Leukotriene B4; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006861:Hydrogen Peroxide; D011464:Epoprostenol; D001241:Aspirin