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

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 micrograms/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 micrograms/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.