Generation of chemotactic activity for neutrophils by liver cells metabolizing ethanol |
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Authors: | F J Roll M Alexander H D Perez |
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Institution: | Department of Medicine, University of California Medical Service, San Francisco General Hospital 94110. |
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Abstract: | The mechanism of polymorphonuclear leukocyte (PMN) infiltration of the liver in acute alcohol-related liver injury is unknown. We have reported that ethanol metabolism by hepatocytes incubated with moderate concentrations of ethanol (2-50 mM) results in the release into the medium of a chemoattractant for human PMN. This response to ethanol is time- and concentration-dependent with peak activity at 10 mM ethanol. Generation of the factor is specific for hepatocytes and is blocked by inhibiting ethanol metabolism with 4-methylpyrazole. It does not appear to be due to cell death. The activity has been partially characterized: it behaves as a polar lipid, possibly an arachidonic acid metabolite distinct from leukotriene B4. Preliminary studies indicate that a cell-free system derived from liver generates a similar activity. In that system scavengers of oxygen-derived free radicals block production of the factor. |
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