PROTEIN-A INDUCES NO PRODUCTION - INVOLVEMENT OF TYROSINE KINASE, PHOSPHOLIPASE-C, AND PROTEIN-KINASE-C

Protein A of S. aureus exhibits a wide array of immunopotentiating act ivities. Since the role of nitric oxide (NO) in bioregulation has been well envisaged, we studied the effect of Protein A on NO production b y immunocytes both in vivo and in vitro. Our data indicate that PA at a comparable dose of LPS (lipopolysaccharide) increases the NO levels in the serum of Swiss albino mice by about 12-fold from its basal leve l. The peak level is reached at about 12 hours after i.p. inoculation of PA. However, NO concentration returns to the basal value 15 hours p osttreatment. Splenic lymphocytes and peritoneal macrophages showed ap preciable increase in NO production when cultured with PA in vitro. In terestingly, inhibitors of tyrosine kinase, phospholipase C, and prote in kinase C (PKC) inhibited NO production in splenic lymphocytes. Thus , it appears that these enzymes participate in the signaling cascade i nduced by PA, which culminates in the production of NO downstream of P HC. It is possible that PA-induced NO production may have relevance wi th the anti-tumor and anti-parasitic properties of PG described earlie r, (C) 1998 Academic Press.