title: Enhanced early vascular permeability in gelatinase B (MMP-9)-deficient mice: putative contribution of COX-1-derived PGE2 of macrophage origin.
abstract: Increased vascular permeability leading to vascular leakage is a central feature of all inflammatory reactions and is critical for the formation of an inflammatory exudate. The leakage occurs because of gap formation between endothelial cells and breakdown of the basement membrane barriers. The present study aimed to investigate the role of gelatinase B [matrix metalloproteinase 9 (MMP-9)], known to be involved in neutrophil exudation, in changes of vascular permeability at the early stages of acute zymosan peritonitis. We show that although MMP-9 is being released already within the first minutes of peritonitis, its lack, induced pharmacologically or genetically, does not decrease but rather increases vasopermeability. In mice treated with an inhibitor of gelatinases (A and B), a tendency to increased vasopermeability existed, and in MMP-9-/- mice [knockout (KO)], the difference was statistically significant in comparison with their controls. Moreover, in intact KO mice, significantly augmented production of prostaglandin E(2) (PGE(2)) of cyclooxygenase 1 (COX-1) origin was detected, and depletion 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 PGE(2) by peritoneal macrophages. We conclude that genetic deficiency in gelatinase B might lead to the development of a compensatory mechanism involving the COX pathway.
authors: Department of Evolutionary Immunobiology, Institute of Zoology, Jagiellonian University, ul. Ingardena 6, PL-30-060 Krakow, Poland. kolac@zuk.iz.uj.edu.pl
authors: Elzbieta
authors: E
authors: Kolaczkowska
authors: Anna
authors: A
authors: Scislowska-Czarnecka
authors: Magdalena
authors: M
authors: Chadzinska
authors: Barbara
authors: B
authors: Plytycz
authors: Nico
authors: N
authors: van Rooijen
authors: Ghislain
authors: G
authors: Opdenakker
authors: Bernd
authors: B
authors: Arnold