Transcellular biosynthesis of lipoxin A4 during adhesion of platelets and neutrophils in experimental immune complex XXXX .

@entity32 @entity1426 @entity73254 @entity35 @entity1813 @entity631
Polymorphonuclear neutrophils are important effectors of @entity32 . Many inflammatory diseases are self-limiting, raising the possibility that compounds are generated in vivo during the course of @entity32 that inhibit neutrophil recruitment and tissue destruction. Lipoxins, a more recent addition to the families of bioactive @entity1813 , are potential candidates in this regard. Lipoxins are generated via pathways that initially involve the dual lipoxygenation of @entity1426 and are potent inhibitors of several neutrophil trafficking events in vitro. Here, we present evidence that lipoxin A4 is generated in @entity35 kidneys during experimental immune complex-mediated @entity631 in vivo. Renal lipoxin A4 levels were markedly reduced by prior depletion of animals of either neutrophils or platelets, suggesting that most lipoxin A4 generated in vivo was derived from transcellular biosynthetic pathways during platelet-neutrophil interactions. Electron microscopic examination of glomerulonephritic kidneys revealed areas of intimate contact between neutrophils and platelets within the lumen of glomerular capillaries. P-selectin on platelets is an important mediator of platelet-neutrophil adhesion in vitro and in vivo. Prior treatment of animals with a blocking monoclonal antibody (mAb) against P-selectin (mAb @entity73254 ), but not an isotype-matched non-blocking control mAb (mAb PNB1.6), caused striking inhibition of lipoxin A4 generation without attenuating neutrophil recruitment. Anti-P-selectin mAb also blunted transcellular lipoxin A4 generation during coincubations of activated neutrophils and platelets in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
