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

Kidney International
A PapayianniH R Brady

Abstract

Polymorphonuclear neutrophils are important effectors of injury in host defense and inflammation. Many inflammatory diseases are self-limiting, raising the possibility that compounds are generated in vivo during the course of inflammation that inhibit neutrophil recruitment and tissue destruction. Lipoxins, a more recent addition to the families of bioactive eicosanoids, are potential candidates in this regard. Lipoxins are generated via pathways that initially involve the dual lipoxygenation of arachidonic acid and are potent inhibitors of several neutrophil trafficking events in vitro. Here, we present evidence that lipoxin A4 is generated in rat kidneys during experimental immune complex-mediated glomerulonephritis 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 adhesi...Continue Reading

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