Studies on the release of cell-associated interleukin 1 by paraformaldehyde-treated murine macrophages.

Experiments are presented demonstrating the release of interleukin 1 (IL1) by lipopolysaccharide-stimulated murine macrophages (M phi) after treatment of the cells with paraformaldehyde (PFA). The IL1 activity set free was completely blocked by a rabbit anti-mouse IL1 alpha antiserum. Immunoprecipitation studies revealed that the IL1 released was of Mr 33 kDa, 23 kDa and 17 kDa. Incubation of PFA-treated M phi in the presence of leupeptin reduced the amount of detectable low molecular mass (i.e. 23 kDa and 17 kDa) IL1 alpha. Addition of leupeptin to PFA-treated M phi also reduced the amount of released IL1 activity, suggesting that proteolytic modification of the IL1 alpha precursor is involved in the generation of biological active IL1 alpha. It is proposed that the cell-associated 33-kDa IL1 is released from the M phi by vesiculation of parts of the M phi cell membrane, followed by a proteolytic cleavage step.