Interferon-gamma augments hydrolysis of LTA4 to LTB4 by endothelial cells.
LTB4 is a potent mediator of inflammation acting at local sites of inflammation. LTB4 increases the lymphocyte binding to and penetration through the endothelium. In this paper we demonstrate that while endothelial cells were unable to metabolize LTB4 from arachidonic acid they were able to hydrolyse LTA4 into LTB4 in a granulocyte-endothelial co-culture assay. This hydrolysis is markedly increased if endothelial cells were pretreated with IFN-gamma prior to the assay. The IFN-gamma induced effect was shown to be time- and dose-dependent. The ability of endothelial cells to hydrolyse LTA4 to LTB4 may provide an answer how LTB4 can be produced in large quantities by nonheamatopoetic cells (i.e. by endothelial cells) at sites of acute inflammation.
Renkonen
R
R
Transplantation Laboratory, University of Helsinki, Finland.
Ustinov
J
J
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006868:Hydrolysis; D066298:In Vitro Techniques; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007371:Interferon-gamma / Q000494:pharmacology*; D017572:Leukotriene A4; D007975:Leukotriene B4 / Q000096:biosynthesis*; D015289:Leukotrienes / Q000378:metabolism*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D017572:Leukotriene A4; D015289:Leukotrienes; D007975:Leukotriene B4; D007371:Interferon-gamma