Journal of the American Society of Nephrology, Vol 3, 907-915, Copyright © 1992 by American Society of Nephrology

EDITORIALS

Five-lipoxygenase products in glomerular immune injury

KF Badr

Leukocyte infiltration, proliferation, and activation are central pathogenetic components of immune injury in the glomerulus. Initial cellular infiltration by polymorphonuclear leukocytes (PMN) is a consequence of the deposition of immune complexes at discreet sites in the glomerulus. This is often followed by macrophage/monocyte infiltration, as well as proliferation of resident mesangial macrophages. Activated leukocytes constitute a rich source of lipid- derived bioactive autacoids, in particular, oxygenated metabolites of arachidonic acid. Here, we assess the role of the five-lipoxygenase (5- LO) family of eicosanoids, in particular, leukotrienes D4 and B4 (LTD4 and LTB4) in mediating functional and structural deterioration during immune inflammatory reactions in the glomerulus. LTD4 and other peptidyl LT appear to play a central role in the reductions in GFR in the acute phases of injury by virtue of their potent vasoactive properties, in particular, their capacity to reduce the glomerular capillary ultrafiltration coefficient, likely through contraction of smooth muscle elements in glomerular mesangial cells. The latter cells possess specific receptors for LTD4 in both humans and rat and contract in vitro when exposed to LTD4 after receptor-mediated activation of phospholipase C. LTB4, a nonvasoconstrictor LT, is released in the early phases of immune injury, likely from leukocyte sources as well as from transcellular metabolism of its precursor, LTA4, by the enzyme LTA4-hydrolase in glomerular mesangial and endothelial cells. LTB4, a potent promoter of PMN attraction, adhesion, and activation exacerbates glomerular functional impairment and structural damage by amplifying PMN-dependent mechanisms of injury. In their totality, 5-LO products of arachidonic acid contribute to the impairment of the normal glomerular filtration and sieving functions that attend acute inflammatory injury in the renal glomerulus and to the subsequent progression of glomerular destruction. This is high-lighted by the significant degree of protection afforded by the selective inhibition of arachidonate 5-LO in vivo in acute and chronic models of experimental glomerulonephritis.

This article has been cited by other articles:

				S. W. Reinhold, H. Vitzthum, T. Filbeck, K. Wolf, C. Lattas, G. A. J. Riegger, A. Kurtz, and B. K. Kramer Gene expression of 5-, 12-, and 15-lipoxygenases and leukotriene receptors along the rat nephron Am J Physiol Renal Physiol, April 1, 2006; 290(4): F864 - F872. [Abstract] [Full Text] [PDF]

				E. Noiri, T. Yokomizo, A. Nakao, T. Izumi, T. Fujita, S. Kimura, and T. Shimizu An in vivo approach showing the chemotactic activity of leukotriene B4 in acute renal ischemic-reperfusion injury PNAS, January 18, 2000; 97(2): 823 - 828. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673