DISCORDANCE BETWEEN MACROPHAGE ARACHIDONATE METABOLIC PHENOTYPE AND THE EXPRESSION OF CYTOSOLIC PHOSPHOLIPASE A(2) AND CYCLOOXYGENASE

Macrophages (M phi s) exhibit variations in their ability to release a nd metabolize arachidonate (AA) depending on their state of activation , differentiation, and tissue origin. In order to understand these var iations on a molecular level, we determined whether differences in AA release and metabolism by murine peritoneal M phi s could be explained in terms of cytosolic phospholipase A(2) (cPLA(2)) and cyclooxygenase (COX) expression. Resident M phi s exhibited greater COX capacity (co nversion of exogenous AA to PGE(2)) but lower phospholipase (PLase) ac tivity (release of endogenous AA) than elicited M phi s. Activation of resident M phi s in vivo with endotoxin increased both their PLase ac tivity and COX capacity. Despite the observed differences in PLase act ivity, peritoneal M phi s under all conditions expressed similar amoun ts of cPLA, mRNA and protein. All M phi s exhibited COX-1 mRNA and pro tein (i.e., the constitutive isoform of COX), although elicited M phi s exhibited increased mRNA for COX-I but decreased levels of protein, relative to resident M phi s. Elicited (but not resident) cells also e xhibited COX-2 mRNA but not COX-2 protein (i.e., the inducible form of COX). Despite the increased COX capacity of resident cells with in vi vo activation, their expression of COX-2 mRNA and protein was equivale nt to that of unactivated cells, becoming apparent only after cell adh erence in vitro. In sum, there is no simple relationship between the a bility of M phi s to release and metabolize AA, and the expression of cPLA(2) or COX isoforms. Moreover, adherence appears to be important f or the expression of COX-2 by M phi s.