Arachidonic acid and leukotriene B4 induce aggregation of human peripheral blood mononuclear leucocytes in vitro.
Peripheral human blood mononuclear leucocytes (MNL) aggregated in response to arachidonic acid (AA) in vitro. This phenomenon was similar to that already described for polymorphonuclear cells (PMN). The effect of AA was concentration-dependent and was shared only by the structurally related di-homo-gamma-linolenic acid among the other fatty acids tested. A number of agents able to induce platelet aggregation such as ADP, collagen, serotonin and a stable prostaglandin analogue all failed to stimulate MNL or PMN aggregation. Inhibitors of cyclo-oxygenase activity such as acetylsalicylic acid and indomethacin not only did not prevent AA-induced aggregation, but even potentiated it. In contrast, both nordihydroguaiaretic acid and BW 755C, two inhibitors of cyclo-oxygenase and lipoxygenase, strongly prevented MNL aggregation. Thus AA seems to aggregate MNL through the mediation of lipoxygenase products. This is supported by the observation that leukotriene B4 (LTB4) also induced MNL aggregation. When highly purified lymphocyte and monocyte preparations were assessed separately, the latter responded to AA similarly to mixed MNL whereas lymphocyte aggregation was inconsistent, small and reversible even at high concentrations of AA. Although the pathophysiological significance of the MNL aggregation described here is still obscure, assembly of these cells--particularly monocytes--at the site of injury might be a crucial event.
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D015126:8,11,14-Eicosatrienoic Acid / Q000494:pharmacology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D002396:Catechols / Q000494:pharmacology; D002449:Cell Aggregation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D007975:Leukotriene B4 / Q000494:pharmacology*; D009637:Masoprocol; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D011720:Pyrazoles / Q000494:pharmacology
D001095:Arachidonic Acids; D002396:Catechols; D011720:Pyrazoles; D007975:Leukotriene B4; D016718:Arachidonic Acid; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D009637:Masoprocol; D015126:8,11,14-Eicosatrienoic Acid; D001241:Aspirin; D007213:Indomethacin