ACTIVATION OF HUMAN BASOPHILS BY STAPHYLOCOCCAL PROTEIN-A .1. THE ROLE OF CYCLIC-AMP, ARACHIDONIC-ACID METABOLITES, MICROTUBULES AND MICROFILAMENTS

Abstract

Protein A from Staphlococcus aureus (Staph A) induces histamine secretion from human basophil leukocytes in the concentration range 10-4-10 .mu.g/ml. This reaction has great similarities to that of antigen or anti-IgE-induced release. It is characterized by a 2 stage reaction, requires extracellular Ca and is optimal at 37.degree. C. The rate of release is similar to that of IgE-mediated reactions. Histamine release induced by Staph A is inhibited by metabolic inhibitors [2-deoxy-D-glucose, antimycin A] drugs which increase intracellular cAMP levels [dibutyryl cAMP, 3-isobutyl-1-methylxanthine, prostaglandin E2, dimaprit], inhibitors of lipoxygenase pathways [5,8,11,14-eicosatetraenoic acid, 5,8,11-eicosatriynoic acid] and a phospholipase A2 inhibitor [p-bromophenacyl bromide]. D2O and cytochalasin B which affect microtubules and microfilaments, respectively, enhance histamine release induced by Staph A. Evidently, staph A-induced release is modulated by intracellular cAMP, arachidonic acid metabolites, requires energy and is enhanced by the disruption of microfilaments and stabilization of microtubules.