PROHORMONE CONVERTASES PC2 AND PC3 IN RAT NEUTROPHILS AND MACROPHAGES- PARALLEL CHANGES WITH PROENKEPHALIN-DERIVED PEPTIDES INDUCED BY LPSIN-VIVO

Prohormone- or proneuropeptide-converting enzymes PC2 and PC3 have bee n observed exclusively in nervous and endocrine tissues. In this work the presence of these enzymes in cells of the immune system was demons trated. PC2 was detected in peripheral and liver-infiltrating polymorp honuclear leukocytes (PMN) but not in alveolar macrophages (AM) or spl een mononuclear cells (SMC). PC2 protei ns corresponded to 75, 71 and 56 kDa forms. PC3 appeared in AM and SMC but not in PMN, and a 66 kDa protein was the only PC3 form detected. Proenkephalin-derived peptides (PENKp) were observed in PMN and AM, showing peptides of 35, 28, 21, 18 and 14 kDa in the former cells and a doublet of 35 and 32 kDa in th e latter. PC2 proteins and PENKp decreased in liver PMN and peripheral PMN 90 min after intravenous (i.v.) infusion of LPS, suggesting an in creased release. However, in vitro assays showed that the chemotactic peptide FMLP but not LPS increased the basal secretion of PC2 proteins and PENKp in PMN. These results indicate that PC2 proteins are releas ed from PMN, together with PENKp, and suggest that LPS in vivo may act through an indirect mechanism. Low levels of PC3 and PENK were detect ed in the AM of rats treated for 90 min with SAL or LPS. However, a si gnificant increase of PC3 and PENKp appeared 30 h after LPS infusion. These results show for the first time that PC2 and PC3 are differentia lly expressed in PMN and AM, respectively, which were paralleled by th e presence of different post-translational products of PENK. In additi on, the in vivo effect of LPS on PC2, PC3 and PENKp levels in PMN and AM resembles the effect of LPS on prohormone levels in endocrine tissu es, suggesting that similar mechanisms may control the turnover of PEN K in endocrine and in these immune cells.