Paf-acether (platelet-activating factor) and interleukin-1-like cytokine production by lipopolysaccharide-stimulated glomeruli

Abstract The production of inflammatory mediators by glomerular cells may be instrumental in the development of pathophysiological alterations during glomerulonephritis. Since bacterial lipopolysaccharide (LPS) is a naturally occurring immunological stimulus, we studied its inflammatory effects on isolated renal glomeruli. LPS stimulation of human and rat isolated glomeruli resulted in a dose-and time-dependent platelet-activating factor (paf-acether) production. Maximal paf-acether generation (1.04 to 1.50 ng/mg protein) ( n = 18 ) was obtained when glomeruli were stimulated for periods of 1 to 4 hr and with 1–2 μg/ml LPS. Paf-acether derived from human and rat glomeruli exhibited identical biological and physicochemical characteristics. In addition, rat glomeruli stimulated with doses of LPS from 100 ng to 50 μg/ml released an Interleukin-1 (IL-1)-like cytokine differing in part from that described in cultured mesangial cells. Maximal release of IL-1-like activity by rat glomeruli was obtained after 24 to 48 hr incubation in the presence of LPS, After gel chromatography resolution, the glomerular cytokine presented IL-1-like activity in fractions corresponding to molecular weights of 15–35 and 4–8 kDa. The latter compounds could represent metabolites similar to those described in normal urine. Thus the local release of paf-acether and IL-1-like cytokine by glomeruli in response to bacterial stimuli may represent a prominent feature of glomerular inflammation.