Neutrophil adhesion to glomerular mesangial cells: regulation by lipoxygenase-derived eicosanoids.
Our results suggest that leukotrienes promote rapid PMN adhesion to glomerular mesangial cells via actions on PMN (LTB4) and mesangial cells (LTD4). Leukotriene-induced adhesion appeared to be mediated by a CD11/CD18-dependent (LTB4) and -independent (LTD4) mechanisms. The specific epitopes mediating LTD4-induced adhesion remain to be defined. Lipoxins did not influence basal adhesion. In contrast, lipoxins markedly inhibited LTD4-, but not LTB4-induced responses. Further elucidation of the components of these adhesion processes, of the pathways for leukotriene and lipoxin biosynthesis in the inflamed glomerulus, and of the counterregulatory actions of lipoxins and leukotrienes may reveal sites for therapeutic intervention in GN. (graph; see text) Data are mean +/- SE of 3 experiments, each conducted in quadruplicate. Leukotriene-induced adhesion was not inhibited by vehicle alone.
Brady
H R
HR
Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115.
Denton
M D
MD
Brenner
B M
BM
Serhan
C N
CN
D000704:Analysis of Variance; D002448:Cell Adhesion; D002449:Cell Aggregation; D002478:Cells, Cultured; D015777:Eicosanoids / Q000502:physiology*; D005920:Glomerular Mesangium / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D005921:Glomerulonephritis / Q000503:physiopathology; D006801:Humans; D015289:Leukotrienes / Q000494:pharmacology*; D008084:Lipoxygenase / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*
D015777:Eicosanoids; D015289:Leukotrienes; D008084:Lipoxygenase