Endothelial cell-associated platelet-activating factor primes neutrophils for enhanced superoxide production and arachidonic acid release during adhesion to but not transmigration across IL-1 beta-treated endothelial monolayers.
The role of platelet-activating factor (PAF) in stimulating neutrophils during interaction with HUVEC has been investigated using the specific PAF receptor antagonists WEB 2086 and YM 264. PAF antagonists at concentrations up to 40 microM had little effect on the adhesion of neutrophils to control or IL-1 beta-stimulated HUVEC monolayers. However, polarization of neutrophils on adhesion to IL-1-treated HUVEC was markedly diminished in the presence of PAF antagonists. In addition, the PAF antagonists WEB 2086 and YM 264 strongly inhibited the migration of neutrophils across IL-1-treated endothelial monolayers. Priming of neutrophil respiratory burst and arachidonic acid release caused by contact with IL-1-treated endothelial cells was also inhibited by PAF antagonists. However, priming as a consequence of transmigration was not inhibited by either WEB 2086 or YM 264. These results suggest that HUVEC-associated PAF plays a central role in the polarization and subsequent transmigration of neutrophils during interaction with HUVEC monolayers. Moreover, the results further suggest that PAF is responsible for priming neutrophils during contact with HUVECs. However, after transmigration, factors other than PAF are responsible for the priming of neutrophil function.
Hill
M E
ME
Yamanouchi Research Institute, Littlemore Hospital, Oxford, UK.
Bird
I N
IN
Daniels
R H
RH
Elmore
M A
MA
Finnen
M J
MJ
D016718:Arachidonic Acid / Q000378:metabolism; D001381:Azepines / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D018375:Neutrophil Activation; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D007375:Interleukin-1; D010879:Piperazines; D010972:Platelet Activating Factor; D013844:Thiazoles; D053778:Thiazolidines; D014230:Triazoles; C052518:WEB 2086; D013481:Superoxides; C068679:YM 264; D016718:Arachidonic Acid