Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recruitment of inflammatory cells to the lung capillaries has been proposed as an important step in the sequence of events that lead to acute lung injury. Frequently, in the clinical setting, bacteremia and sepsis syndrome precede the acute lung failure and endotoxin priming may represent a comparable paradigm, useful for experimental pursuit. Following addition of the chemotactic tripeptide FMLP (10(-9) to 10(-6) M) to the cell-free, salt solution perfusate of isolated rat lungs, only a small degree of vasoconstriction was observed. However, in lungs isolated from rats that received 2 mg/kg intraperitoneal Salmonella enteritidis endotoxin 2 h before lung perfusion, FMLP dose dependently caused a large, transient pulmonary pressor response, edema formation, and release of large amounts of thromboxane and leukotriene B4. Since in vitro priming with endotoxin, direct vascular injury by neutrophil elastase, nor direct stimulation with FMLP of pulmonary artery rings from endotoxin-pretreated rats, mimicked the effects of in vivo endotoxin priming, we conclude that the presence of inflammatory cells in the lung capillaries accounted for the large amount of eicosanoids produced by the lungs after FMLP stimulation. In fact, by retrograde lavage of the lung circulation with a collagenase solution, previously adherent cell clumps were mobilized and identified. These cell clumps, composed of red blood cells, neutrophils, and platelets, were not seen in the vascular lavage sediment obtained from unprimed control lungs. Indomethacin, a thromboxane antagonist, AA861, a 5-lipoxygenase inhibitor, and WEB 2086, a platelet-activating factor (PAF) antagonist, reduced the thromboxane synthesis and release after FMLP (10(-7) M) in in vivo endotoxin-primed lungs. None of the inhibitors employed exclusively inhibited only one particular eicosanoid mediator but rather affected the release of several mediators, suggesting a close link between the different synthetic arachidonic acid pathways. An inhibitor of phospholipase C (2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate), NCDC, but not an inhibitor of phospholipase D (Wortmannin) or of protein kinase C (staurosporine) inhibited the FMLP-stimulated pulmonary pressure rise and eicosanoid release in endotoxin-primed lungs in vivo. Our data suggest that eicosanoids (in particular thromboxane) released from cells trapped in the lung circulation, but not from constitutive lung cells, contribute to vasoconstriction and edema formation caused by the chemoattractant FMLP in endotoxin-primed lungs.
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PMID:FMLP causes eicosanoid-dependent vasoconstriction and edema in lungs from endotoxin-primed rats. 154 53

A study was conducted to investigate production rate of leukotriene B4 (LTB4) in parenchymal and sinusoidal liver cells of rats with acute hepatic failure (AHF). AHF was induced by simultaneous administration of D-galactosamine (GalN) and endotoxin (LPS), and parenchymal as well as sinusoidal liver cells were isolated by collagenase perfusion method. Following preincubation for 15 min, isolated cellular fractions were incubated with Ca-ionophore (2 microM) for 5 min, and levels of LTB4 in culture media before and 5 min after addition of Ca-ionophore were analyzed by HPLC. Following results were obtained: The production rate of LTB4 was found to be the highest in Kupffer cells (7.2ng/10(6) cells/5 min), followed by endothelial cells (1.1), stellate cells (0.2) and parenchymal cells (not detectable). The production rate of LTB4 in both Kupffer cells and endothelial cells was found to reach a maximum in the fraction isolated 60 min after administration of GalN and LPS. Treatment with AA861, one of the selective inhibitors of 5-lipoxygenase, was shown to reduce the production of LTB4 in Kupffer cells to 53% at 10(-7)M and above 99% at higher than 10(-5)M. In conclusion, the majority of LTB4 generated in the liver of rats with AHF was found to be synthesized in Kupffer cells and, to a lesser extent, in endothelial cells, and the enhanced production of LTB4 was found to be greatly inhibited by treatment with AA861.
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PMID:Production of leukotriene B4 in parenchymal and sinusoidal cells of the liver in rats treated simultaneously with D-galactosamine and endotoxin. 255 38