Evidence for a platelet-activating factor receptor on human alveolar macrophages.
In this report we demonstrate evidence which strongly suggests that human alveolar macrophages possess receptor for the platelet activating factor (PAF). We investigated the effects of PAF by measuring (a) the intracellular free calcium concentration [Ca2+]i, using the fura-2 method in single isolated cells and (b) the production of superoxide anion. PAF increased [Ca2+]i in a dose-dependent manner (EC50 = 1 x 10(-8) M), whereas lyso-PAF had no effect. The initial increase of [Ca2+]i was followed by a slow decrease to a sustained elevation of [Ca2+]i significantly above basal values. While the initial rise in [Ca2+]i was only slightly reduced in Ca(2+)-free medium (1 mM EGTA), the sustained phase was totally abolished. The sustained calcium increase was also blocked after preincubation of AM with the calcium-channel blocker nitrendipine. PAF increased the production of superoxide anion (O2-) by human alveolar macrophages in a dose- dependent manner. The effects of PAF on [Ca2+]i and (O2-) could be blocked by the PAF-specific antagonist WEB 2086 dose dependently, indicating a receptor-mediated event.
Schaberg
T
T
Department of Pneumology, Medizinische Klinik, Universitätsklinikum Steglitz, Freie Universität Berlin, Germany.
Haller
H
H
Lode
H
H
D000328:Adult; D001381:Azepines / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002452:Cell Count; D005260:Female; D016257:Fura-2 / Q000494:pharmacology; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009568:Nitrendipine / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled; D013481:Superoxides / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; C039351:platelet activating factor receptor; C052518:WEB 2086; D013481:Superoxides; D009568:Nitrendipine; D010100:Oxygen; D002118:Calcium; D016257:Fura-2