Early vascular permeability in murine experimental peritonitis is co-mediated by resident peritoneal macrophages and mast cells: crucial involvement of macrophage-derived cysteinyl-leukotrienes.
The initial phase of zymosan-induced peritonitis involves an increase of vascular permeability (peak at 30 min) that is correlated with high levels of vasoactive eicosanoids, namely, prostaglandins (PGI2 and PGE2) of cyclooxygenase-1 origin (as estimated by RT-PCR) and cysteinyl-leukotrienes. Previously, we showed that the increase of vascular permeability can be attributed only partially to mast cells and their histamine, as seen in mast cell-deficient WBB6F1-W/Wv mice. Thus we aimed to identify the major cellular source(s) that mediate vasopermeability, as well as particular vasoactive mediators operating in this model. For this purpose, some mice were selectively depleted of either peritoneal macrophages or mast cells, and/or they were treated with several pharmacologic inhibitors of cyclooxygenase- and lipoxygenase-metabolic pathways. More-over, macrophage-depleted mast cell-deficient WBB6F1-W/Wv mice and their controls (+/+) were used. The macrophage depletion always caused a profound decrease of both vascular permeability and lipid-mediator levels, which was particularly pronounced for leukotrienes, whereas the effects of mast-cell depletion were less severe. The macrophage/mast-cell co-mediation of vasopermeability was also revealed in thioglycolate-induced peritonitis, as well as the macrophage origin of cysteinyl-leukotrienes. Taken together, these findings demonstrate that the resident peritoneal macrophages are in fact the main contributors to the vasopermeability at the early stages of zymosan-induced peritonitis.
Kolaczkowska
Elzbieta
E
Department of Experimental Pathology, Institute of Medical Biology, University of Tromsø, Norway.
Shahzidi
Susan
S
Seljelid
Rolf
R
van Rooijen
Nico
N
Plytycz
Barbara
B
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D019559:Capillary Leak Syndrome / Q000209:etiology / Q000503:physiopathology*; D002199:Capillary Permeability / Q000502:physiology*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003545:Cysteine / Q000378:metabolism*; D004224:Diterpenes; D015777:Eicosanoids / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D046934:Ginkgolides; D006636:Histamine Release; D007211:Indoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D007783:Lactones / Q000494:pharmacology; D017997:Leukotriene C4 / Q000096:biosynthesis; D015289:Leukotrienes / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008407:Mast Cells / Q000378:metabolism / Q000502:physiology*; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D009578:Nitrobenzenes / Q000494:pharmacology; D010538:Peritonitis / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D010742:Phospholipid Ethers / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics; D011804:Quinolines / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013864:Thioglycolates / Q000633:toxicity; D015054:Zymosan / Q000633:toxicity; D002722:Chlorobenzenes
D015121:6-Ketoprostaglandin F1 alpha; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D003545:Cysteine; D004224:Diterpenes; D015777:Eicosanoids; D046934:Ginkgolides; D007211:Indoles; D007213:Indomethacin; D007527:Isoenzymes; D007783:Lactones; D017997:Leukotriene C4; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D008565:Membrane Proteins; D009578:Nitrobenzenes; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D011451:Prostaglandin-Endoperoxide Synthases; D011804:Quinolines; D013449:Sulfonamides; D013864:Thioglycolates; D015054:Zymosan; C112381:cysteinyl-leukotriene; C060893:MK-886; D002722:Chlorobenzenes; C049740:alpha-pentyl-3-(2-quinolinylmethoxy)benzenemethanol; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; C037913:CV 3988; C045856:ginkgolide B; C496512:Ptgs1 protein, mouse; C012655:nimesulide