Modification of the functional activity of neutrophils treated with acute phase response proteins

The effects of alpha1-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 nature, namely, galactose-specific mistletoe (Viscum album) lectin (VAA), digitonin, and N-formyl-Met-Leu-Phe, a chemotactic peptide (FMLP), were studied. Within the concentration range of 13-500 microgram/ml, AGP and its 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 microgram/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 antennae of AGP is not necessary for its inhibitory effect on human neutrophil respiratory burst because asialo-AGP (250 microgram/ml) inhibited H2O2 generation by cells stimulated with agonists of the NADPH-oxidase system of phagocytes. In contrast to AGP, two other acute phase response proteins displaying a lectin activity (C-reactive protein and serum amyloid P component) within the concentration range of 10-100 microgram/ml produced no significant effect on H2O2 generation by stimulated neutrophils. These data suggest that AGP is an effector molecule responsible for feedback regulation of the functional activity of neutrophils.