Adhesion of guinea pig polymorphonuclear leukocytes to autologous aortic strips: influence of chemotactic factors and of pharmacological agents which affect arachidonic acid metabolism.
In superfusion experiments, the complement peptide C5a-desArg and the leukotriene B4 (LTB4) enhanced adhesion of guinea pig polymorphonuclear leukocytes to autologous aortic strips (threshold at about 10(-8) M, maximal effects at 10(-7) M). C5a-desArg acted primarily by stimulation of the leukocytes: pretreatment of them with the peptide abolished their response by deactivation, whereas pretreatment of the endothelium did not affect adhesion. However, the endothelium obviously cooperated in the response: enhanced adhesion was obtained only when the leukocytes were exposed to C5a-desArg while in contact with the endothelium. The cooperation is most probably due to release of arachidonic acid from endothelium and formation of lipoxygenase products (LTB4?) therefrom by the stimulated leukocytes. Incubation of leukocytes with nordihydroguaiaretic acid or with relatively high concentrations of indomethacin--both known to inhibit lipoxygenases-- lowered the effect of C5a-desArg, but not that of LTB4 nor the spontaneous adhesion. On the other hand, the stable prostacyclin analogue ZK 36 374 decreased C5a-desArg-induced adhesion, while pretreatment of the aortic strips with indomethacin increased it. These results suggest that endogenous prostacyclin may also play a role in this system by reducing adhesion.
D000818:Animals; D001011:Aorta / Q000187:drug effects*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects*; D002630:Chemotactic Factors / Q000494:pharmacology; D003182:Complement C5 / Q000494:pharmacology; D015936:Complement C5a; D016861:Cyclooxygenase Inhibitors; D006168:Guinea Pigs; D006801:Humans; D007975:Leukotriene B4 / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors; D008689:Methacrylates / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D001095:Arachidonic Acids; D002630:Chemotactic Factors; D003182:Complement C5; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D008689:Methacrylates; D007975:Leukotriene B4; D016718:Arachidonic Acid; D015936:Complement C5a; D013930:Thromboxane-A Synthase; C034364:ozagrel