Viable rat Kupffer cells synthesize but do not secrete interleukin-1: indications for necrosis-induced maturation of interleukin-1 alpha, but not of interleukin-1 beta.
Interleukin-1 is involved in host defense to infection and injury. In this work synthesis and secretion of IL-1 by cultured rat liver macrophages (Kupffer cells) in response to lipopolysaccharide were investigated. IL-1 was found only intracellularly as 31-kD (pro-IL-1 alpha) and 34-kD (pro-IL-1 beta) proteins. No mature 17-kD IL-1 alpha or IL-1 beta was detected in cell lysates or supernatants. Pulse-chase experiments showed that there was no release of IL-1 even after 24h, although pro-IL-1 continuously disappeared from the cells. Cultures were lysed by freezing-thawing. Pro-IL-1 beta was then found in the supernatants, but pro-IL-1 alpha was processed into several smaller fragments. A 17-kD protein could represent the mature IL-1 alpha. The results indicate that Kupffer cells are not able to secrete biologically active mature IL-1 proteins. By lysis of the cells. IL-1 is released. Pro-IL-1 alpha is processed, but pro-IL-1 beta seems to need further activation processes.
Armbrust
T
T
Department of Gastroenerology and Endocrinology, George-August-University, Göttingen, Germany.
Schmitt
E
E
Ramadori
G
G
D000818:Animals; D001681:Biological Assay; D002460:Cell Line; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000302:isolation & purification; D007700:Kinetics; D007728:Kupffer Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000276:immunology; D051379:Mice; D008970:Molecular Weight; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D009336:Necrosis; D051381:Rats; D017208:Rats, Wistar
D007375:Interleukin-1; D008070:Lipopolysaccharides