Critical role of mast cells in morphine-mediated impairment of zymosan-induced peritonitis in mice

Objective and Design: Zymosan-induced peritoneal inflammation is significan tly inhibited in mice injected with an irritant supplemented with morphine. The aim of the present study was to examine the putative mast cell involve ment in this inhibition. Subjects: Peritonitis was induced in WBB6F1 mice (genetically mast cell-def icient W/W-v and their control littermaters +/+) and in Balb/c mice, with n ormal mast cells (MC) and mast cell-depleted (MCx) by pretreatment with com pound 48/80. Bone marrow leukocytes from intact Balb/c mice were tested for their sensitivity to chemoattractants after in vitro incubation with morph ine (10(-6) M), with or without preincubation with naltrexone (10(-8) M). C ontrol cells were incubated in medium only. Treatment: Peritonitis was induced by i.p. injection of either zymosan only (Z, 2 mg/ml) or zymosan supplemented with morphine (ZM, M: 20 mg/kg), with out or with pretreatment with naltrexone (NZM, N: 5 mg/kg). Methods: Thirty minutes after induction of peritonitis, the histamine level s (ELISA) and vascular permeability (Evans blue leakage) were measured. At 6 h, the number of exudatory leukocytes (haemocytometer) and chemotaxis/che moattractant level (48-well chemotactic chamber) were estimated. Results: (1) At 6 h of peritonitis, the number of exudatory leukocytes and levels of plasma chemoattractants were significantly lower in animals injec ted with zymosan supplemented with morphine (ZM) than in Z and NZM groups o f WBB6F1 and Balb/c mice, but only in those with normal mast cells, and not in their mast cell-deficient/depleted counterparts. (2) In contrast, at 30 minutes, vascular permeability and histamine levels were higher in ZM than in Z group of mice with normal mast cells (MC), but not in those depleted of mast cells (MCx). (3) In vitro preincubation of leukocytes with morphine inhibited their migratory activity only towards peritoneal fluid from zymo san-treated MC mice but not from their MCx counterparts. Conclusions: Mast cell-derived factors are involved in morphine-mediated im pairment of zymosan-induced peritonitis in mice.