Generation of chemotactic activity for neutrophils by liver cells metabolizing ethanol.
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.
Roll
F J
FJ
Department of Medicine, University of California Medical Service, San Francisco General Hospital 94110.
Alexander
M
M
Perez
H D
HD
D000818:Animals; D002630:Chemotactic Factors / Q000096:biosynthesis*; D000431:Ethanol / Q000378:metabolism* / Q000633:toxicity; D005609:Free Radicals; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D009504:Neutrophils / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D002630:Chemotactic Factors; D005609:Free Radicals; D016209:Interleukin-8; D000431:Ethanol; D010100:Oxygen