Journal of Lipid Research, Vol 38, 627-633, Copyright © 1997 by Lipid Research, Inc.
Transcellular metabolism of leukotriene A4 by rabbit blood cells: lack of relevant LTC4-synthase activity in rabbit platelets
A Sala, T Testa, F Nobili and G Folco
Center for Cardiopulmonary Pharmacology, School of Pharmacy, University of Milano, Italy.
The objective of this study was to determine the transcellular metabolism
of leukotriene A4 by rabbit blood cells. mixed peripheral blood leukocyte
preparations with and without platelets in a ratio of 1:40 were challenged
with the Ca(2+)-ionophore A23187. 5-Lipoxygenase metabolites production was
assessed by RP-HPLC coupled with diode-array UV detection. In light of the
observation that leukotriene C4 production in leukocyte-platelet
coincubation was the same as with leukocytes alone, mixed coincubation of
human and rabbit blood cells was tested. Rabbit leukocytes with human
platelets resulted in a significant increase of leukotriene C4 production,
while no changes were observed in human leukocytes with or without rabbit
platelets. In agreement with these results, intact rabbit platelets or
rabbit platelet lysates, unlike human platelets, were not able to convert
synthetic leukotriene A4 free acid to leukotriene C4. These data provide
evidence that rabbit leukocytes are able to make a significant amount of
leukotriene A4 available for transcellular metabolism, while rabbit
platelets, unlike human platelets, lack leukotriene C4-synthase activity.
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