Paf-acether (platelet-activating factor) and interleukin-1-like cytokine production by lipopolysaccharide-stimulated glomeruli.
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.
Morell
G P
GP
INSERM U 200, Université Paris-Sud, Clamart, France.
Pirotzky
E
E
Erard
D
D
Desmottes
R M
RM
Bidault
J
J
Damais
C
C
Benveniste
J
J
D000818:Animals; D005920:Glomerular Mesangium / Q000378:metabolism*; D005921:Glomerulonephritis / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008970:Molecular Weight; D010972:Platelet Activating Factor / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D007375:Interleukin-1; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor