Increased cyclooxygenase-2 and 5-lipoxygenase activating protein expression in peritoneal macrophages during ovalbumin immunization of mice and cytosolic phospholipase A(2) activation after antigen challenge

The present study investigates phenotypic and functional differentiation of peritoneal macrophages during ovalbumin-induced subcutaneous immunization of mice. For the first time we show that, in mouse peritoneal macrophages, ovalbumin immunization induces an increase in cyclooxygenase-2 (COX-2) and 5-lipoxygenase activating protein (FLAP) expression whereas it inhibits cyt osolic phospholipase A(2) (cPLA2) expression. The study of arachidonic acid (AA) metabolism in peritoneal macrophages from control (cPM) and ovalbumin -immunized (iPM) mice shows that the reduced cPLA2 expression is correlated to a reduced basal AA metabolism, but is not a limiting factor for the ops onized zymosan-, PMA-, or A23187-triggered AA metabolism. We also show that in vitro ovalbumin challenge induces, only in iPM, cPLA2 activation throug h phosphorylation of serine residues, via a mechanism involving MAP kinases , and through increased intracellular calcium concentrations, leading to ei cosanoid production. In parallel, we report that, in peritoneal macrophages , ovalbumin immunization induces the expression of CD23, the low affinity r eceptor for IgEs known for its involvement in allergic diseases. Thus, the modified expression of the enzymes involved in AA metabolism and the differ ence of response of cPM and iPM toward the antigen are important elements t o understand the underlying mechanisms of ovalbumin-induced allergic respon ses. (C) 2000 Elsevier Science B.V. All rights reserved.