Stimulation of the scavenger receptor on monocytes-macrophages evokes release of arachidonic acid metabolites and reduced oxygen species.
Mouse peritoneal macrophages are endowed with a scavenger receptor recognizing modified low density lipoproteins (LDL). Metabolic sequelae of receptor occupancy distinct from lipoprotein processing were examined. Adherent peritoneal macrophages were kept in short term culture. Release into culture supernatants of the arachidonic acid derived eicosanoids prostaglandin E, 6-keto-prostaglandin F1a, thromboxane B2, and leukotriene C4 was assessed, and production of reduced oxygen species superoxide anion and hydrogen peroxide, generated in the oxidative burst, was monitored after challenge of macrophages with acetylated or malondialdehyde modified LDL. Modified LDL at concentrations ranging from 50 to 250 micrograms of protein/ml was noted to augment macrophage arachidonic acid metabolism within 6 hours of addition. Cyclo-oxygenase derivatives were synthesized predominantly, but leukotriene C4 generation was also observed. Further, scavenger receptor occupation triggered the release of superoxide anion and hydrogen peroxide which was more rapid in onset and plateaued after 60 minutes of incubation. Human monocyte-derived macrophages, after 4 days in culture, also generated reduced oxygen species and eicosanoids in response to modified LDL. Along with our previous finding of scavenger receptor mediated lysosomal enzyme liberation, the present study indicates novel functions of these binding sites. Our observations may shed new light on the possible role of monocyte-macrophages in atherogenesis.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D010100:Oxygen / Q000378:metabolism; D010529:Peritoneal Cavity / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
D001095:Arachidonic Acids; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D016718:Arachidonic Acid; D010100:Oxygen