MODIFICATION OF THE FUNCTIONAL-ACTIVITY OF NEUTROPHILS TREATED WITH ACUTE-PHASE RESPONSE PROTEINS

The effects of alpha(1)-acidic glycoprotein (AGP) and its subfractions (glycoforms) with different affinity for concanavalin A on generation of H2O2 by human neutrophils exposed to stimulators of different natu re, namely, galactose-specific mistletoe (Viscum album) lectin (VAA), digitonin, and N-formyl-Met-Leu-Phe, a chemotactic peptide (FMLP), wer e studied. Within the concentration range of 13-500 mu g/ml, AGP and i ts glycoforms produced dose-dependent inhibition of digitonin-induced cell responses. AGP also inhibited the VAA-induced generation of H2O2; however, this cell response was potentiated by low concentrations (50 mu g/ml) of AGP and AGP-A. FMLP induced the most consistent response of neutrophils, which changed only slightly in the presence of AGP and AGP-B; however, low concentrations of AGP-A inhibited this response. The presence of sialic acid in the terminal position of carbohydrate a ntennae of AGP is not necessary for its inhibitory effect on human neu trophil respiratory burst because asialo-AGP (250 mu g/ml) inhibited H 2O2 generation by cells stimulated with agonists of the NADPH-oxidase system of phagocytes. In contrast to AGP, two other acute phase respon se proteins displaying a lectin activity (C-reactive protein and serum amyloid P component) within the concentration range of 10-100 mu g/ml produced no significant effect on H2O2 generation by stimulated neutr ophils. These data suggest that AGP is an effector molecule responsibl e for feedback regulation of the functional activity of neutrophils.