ATP induces the release of IL-1 from LPS-primed cells in vivo.
The secretion of IL-1 from murine macrophages in vitro is an inefficient process that is distinct from those of other cytokines such as IL-6. We have therefore studied this process in vivo to see if these differences are maintained. Intraperitoneal injection of LPS in mice induced production and release of IL-6 into the extracellular fluid (peritoneal lavage). Although induction of intracellular IL-1 alpha and IL-1 beta was readily detected, these cytokines were not detected extracellularly. Injection of ATP 2 h after LPS led to the rapid extracellular release of IL-1 beta, IL-1 alpha, lactate dehydrogenase, and beta-N-acetylglucosaminidase. Western blot analysis revealed that a large proportion of the IL-1 beta was released as the 17-kDa form, whereas IL-1 alpha was unprocessed. Adenosine 5'-O-(3-thiotriphosphate) was also effective in causing IL-1 release but not UTP or ADP. This suggests that the ATP-mediated release of IL-1 is a receptor-mediated phenomenon that is associated with cell lysis.
Griffiths
R J
RJ
Department of Immunology and Infectious Diseases, Pfizer Inc., Central Research Division, Groton, CT 06340.
Stam
E J
EJ
Downs
J T
JT
Otterness
I G
IG
D000118:Acetylglucosaminidase / Q000032:analysis; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice
D007375:Interleukin-1; D008070:Lipopolysaccharides; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D000118:Acetylglucosaminidase