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The effect of histamine and leukotriene C4 on the leukocyte activation and adhesion in liver microcirculation was investigated. The hepatic microvasculature was visualized using intravital microscopy to assess the components and mechanisms involved in juxtacrine activation and adhesion of leukocytes. It was found that leukotriene C4 does not activate the known early mechanisms of leukocyte recruitment, including platelet-activating factor, P-selectin or intercellular adhesion molecule-1 in the hepatic microvasculature.

Ostrovsky, Lena, Juliana Carvalho-Tavares, Richard C. Woodman, and Paul Kubes. Translational inhibition of E-selectin expression stimulates P-selectin-dependent neutrophil recruitment. Am J Physiol Heart Circ Physiol 278: H1225-H1232, 2000.--Although known for its role in hemostasis, there is a growing body of evidence that thrombin can induce leukocyte recruitment and contribute to the inflammatory response. An in vitro parallel-plate flow chamber was used to systematically examine thrombin-induced neutrophil interactions with human endothelium. Stimulation of endothelial cells with thrombin (1 U/ml) resulted in an immediate, P-selectin-dependent increase in neutrophil rolling and adhesion that was comparable in magnitude to optimal levels of histamine (the classical inducer of P-selectin). However, thrombin, but not histamine, induced a delayed (4 h) E-selectin-dependent rolling similar to that of tumor necrosis factor-[Alpha], suggesting that thrombin has the unique ability to recruit neutrophils by an early P-selectin and a delayed E-selectin pathway. Surprisingly, inhibition of E-selectin expression with the general protein synthesis inhibitor cycloheximide induced P-selectin expression 4 h after thrombin stimulation. Cycloheximide and thrombin (4 h) induced sufficient P-selectin-dependent rolling to recruit as many neutrophils as were recruited with 4 h of stimulation with thrombin alone. Histamine in the presence of cycloheximide or cycloheximide alone did not evoke the P-selectin response at 4 h, suggesting that this was not due to direct cycloheximide induction of P-selectin. Treatment of endothelium with tumor necrosis factor-[Alpha] (an E-selectin inducer) and cycloheximide also eliminated E-selectin expression but, much like thrombin, induced P-selectin expression and neutrophil recruitment. In conclusion, inhibition of E-selectin via protein synthesis inhibition activates the protein synthesis-independent pathway of P-selectin expression to support adequate leukocyte recruitment. leukocytes; endothelium; adhesion molecules; thrombin; tumor necrosis factor