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