MICROTUBULE-ACTIVE AGENTS MIMIC LIPOPOLYSACCHARIDES IN PRIMING MACROPHAGES FOR ENHANCED ARACHIDONIC-ACID METABOLISM

Macrophages play a crucial role in inflammation and host de defense, i n part, by secreting metabolites of arachidonic acid (20:4). Bacterial lipopolysaccharides (LPS) are poor agonists of the 20:4 cascade, but do have the capacity to prime macrophages for greatly increased 20:4 m etabolism upon subsequent stimulation with activators of protein kinas e C (PKC). The microtubule-stabilizing agent, taxol, mimics many of th e effects of LPS in macrophages. We demonstrate in this study that tax ol, like LPS, primes murine peritoneal macrophages for an enhanced rel ease of 20:4 in response to both phorbol 12-myristate 13-acetate (PMA) and zymosan. Taxol and LPS, when used at maximum concentrations, acte d additively to prime macrophages for PMA-stimulated release of 20:4, suggesting that the two agents signal through different pathways. Inte restingly, agents that stimulate the depolymerization of microtubules, colchicine and nocodazole, also primed macrophages for an enhanced re lease of 20:4 in response to PMA, however, they did not prime when zym osan was the stimulus. We conclude that agents that disrupt the microt ubule network prime resident peritoneal macrophages for enhanced relea se of 20:4. (C) 1996 Wiley-Liss, Inc.