LIPOPOLYSACCHARIDE INDUCES ACTIVATION OF CD14-ASSOCIATED PROTEIN-TYROSINE KINASE P53 56LYN/

Bacterial lipopolysaccharide (LPS) induces a pleiotropic activation of the immune system which might subsequently result in septic shock. On e of the cell surface receptors for LPS is the glycophosphatidylinosit ol-anchored protein CD14. Binding of LPS to CD14 induces production of lymphokines such as tumor necrosis factor-alpha (TNF-alpha), interleu kin-1 (IL-1), IL-6, and IL-8, and CD14 is subsequently released from t he cell surface. However, the mechanism of signaling via CD14 is still not known. We report here that protein tyrosine kinase (PTK) p56lyn i s coupled to the LPS receptor CD14 in human monocytes. LPS rapidly act ivates CD14-associated p56lyn simultaneously with PTKs p58hck and p59c -fgr. Inhibition of PTKs by herbimycin A completely blocks LPS-induced down-modulation of CD14 and production of TNF-alpha and IL-1. These d ata suggest a critical role of PTKs in the LPS/CD14-mediated signal tr ansduction pathway in human monocytes.