Modification of the Functional Activity of Neutrophils Treated with Acute Phase Response Proteins

A. V. Timoshenko¹, N. V. Bovin^2*, S. D. Shiyan², S. Yu. Vakhrushev¹, S. André³, and H.-J. Gabius³

¹Department of Biophysics, Belarussian State University, pr. F. Skoriny 4, Minsk, 220050 Belarus; fax: (375-17) 220-74-65; E-mail: timoshenko@phys.bsu.unibel.by

²Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow, 117871 Russia; fax: (095) 330-5592; E-mail: bovin@ibch.siobc.ras.ru

³Institute of Physiological Chemistry, Munich University, Veterinarstrasse 13, Munich, 80539 Germany; fax: (089) 2180-2508

^* To whom correspondence should be addressed.

Received September 1, 1997

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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 µg/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 µg/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 µg/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 µg/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.

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KEY WORDS: alpha₁-acidic glycoprotein, lectins, hydrogen peroxide, neutrophils

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