Priming of phagocytes by cytokines and water-soluble products of lipid peroxidation.

Abstract

It is well known that during certain pathological processes phagocytes acquire the ability to generate activated oxygen species during phagocytosis. The priming of phagocytes by cytokines and water-soluble products of lipid peroxidation (LPO) is described. Preincubation of human polymorphonuclear leukocytes (PMNL) with the water-soluble products of LPO or oxidised liposomes for 15-20 min at 37 degrees C enhanced their functional activity when they were stimulated by opsonised zymosan or latex particles. There was a 2-3-fold increase in luminol-dependent chemiluminescence response of cells stimulated in this way, and an increase in Fc-receptor expression on the PMNL surface. An endogenous cytokine alone did not activate the phagocytes for an oxidative burst response, but preincubation of murine peritoneal macrophages (MP) and human PMNL with cytokines (molecular mass 20-30 kDa) for 3-48 h at 37 degrees C enhanced the cell chemiluminescence response to opsonised zymosan by a factor of 5-9 for MP and a factor of 2-3 for PMNL. Treatment of phagocytes with the cytokine complex also increased other effector functions of the phagocytes such as tumouricidal activity, phagocytosis, secretion of interleukin-1, and antiparasitic activity. The protein synthesis inhibitor cycloheximide abolished cytokine-induced priming of MP (but not of PMNL). The mechanisms of short-term and prolonged priming of the two types of phagocytes (MP and PMNL) are discussed.