Met-Enkephalin Involvement in Morphine-Modulated Peritonitis in Swiss Mice

Morphine coinjection with zymosan inhibits pain and leukocyte accumulation during peritonitis in several strains of mice, and affects systems of endogenous opioids. Present investigations focus on Met-enkephalin (Met-ENK) in the inflamed peritoneal cavity and brain centers of Swiss mice. Males of Swiss mice were IP injected with zymosan or zymosan supplemented with morphine. At the selected time points the peritoneal leukocytes were counted and the Met-ENK level was measured in exudatory fluid and leukocytes, striatum, hypothalamus, and pituitary gland. The Met-ENK content in peritoneal fluid rised sharply after zymosan injection, which corresponded with its decline in exudatory leukocytes, hypothalamus, and striatum. Morphine coinjection enhanced intraperitoneal accumulation of Met-ENK and its release from exudatory leukocytes, but inhibited its early fluctuations in hypothalamus and striatum. Effects of morphine-modulated inflammation on the Met-ENK system lasted longer than 7 days

Enhanced early vascular permeability in gelatinase B (MMP-9)-deficient mice : putative contribution of COX-1-derived PGE2PGE_{2} of macrophage origin

Abstract: Increased vascular permeability lead-ing to vascular leakage is a central feature of all inflammatory reactions and is critical for the for-mation of an inflammatory exudate. The leakage occurs because of gap formation between endothe-lial cells and breakdown of the basement mem-brane barriers. The present study aimed to inves-tigate the role of gelatinase B [matrix metallopro-teinase 9 (MMP-9)], known to be involved in neutrophil exudation, in changes of vascular per-meability at the early stages of acute zymosan peri-tonitis. We show that although MMP-9 is being released already within the first minutes of perito-nitis, its lack, induced pharmacologically or genet-ically, does not decrease but rather increases va-sopermeability. In mice treated with an inhibitor of gelatinases (A and B), a tendency to increased va-sopermeability existed, and in MMP-9/ mice [knockout (KO)], the difference was statistically significant in comparison with their controls. More-over, in intact KO mice, significantly augmented production of prostaglandin E2 (PGE2) of cycloox-ygenase 1 (COX-1) origin was detected, and deple-tion of peritoneal macrophages, but not mast cells, decreased vasopermeability in KO mice. Thus, the increase of vasopermeability observed on KO mice is a result of the increased production of COX-1-derived PGE2 by peritoneal macrophages. We con-clude that genetic deficiency in gelatinase B might lead to the development of a compensatory mech-anism involving the COX pathway. J. Leukoc. Biol