Alpha 1-acid glycoprotein-induced tumor necrosis factor-alpha secretion ofhuman monocytes is enhanced by serum binding proteins and depends on protein tyrosine kinase activation

The acute phase protein, oil acid glycoprotein (AGP), stimulated human mono nuclear cells as well as monocytes to secrete tumor necrosis factor-alpha ( TNF alpha) which was demonstrated by ELISA, RT-PCR and functional assays. A GP-induced TNFa secretion of monocytes was enhanced in the presence of huma n plasma and inhibited by protein kinase inhibitors, indicating it is serum and tyrosine kinase dependent. The activation of tyrosine kinase in AGP-st imulated monocytes was further confirmed by immunoblotting of tyrosine phos phorylated proteins of monocytes at different time after AGP stimulation. F urthermore, several serum proteins such as C3, sCD14 and IgG were able to b ind to AGP and enhanced TNF alpha secretion of human monocytes induced by A GP. Taken together, these results suggest serum proteins binding to AGP enh ance its ability to stimulate human monocytes to secrete pro-inflammatory c ytokines through a tyrosine kinase dependent pathway. (C) 1999 Elsevier Sci ence B.V. All rights reserved.