Pseudo-alpha(1)-acid glycoprotein with carbohydrate chain ratio typical of native form was synthesized by a previously developed original technique of quantitative transfer of alpha(1)-acid glycoprotein carbohydrate chains to other polymeric carrier. Similarly to native glycoprotein, the semisynthetic analog inhibited lymphocyte proliferation and stimulated the production of antiinflammatory cytokines by peripheral blood mononuclear leukocytes. However, it possessed no antioxidant activity and did not inhibit complement activation by the alternative pathway. The role of carbohydrate and protein components of alpha(1)-acid glycoprotein molecule in the realization of its biological effects is discussed.

The mechanisms of the antiproliferative effect of acacid glycoprotein (AGP) isolated from the blood of healthy donors (nAGP) and from the ascitic fluid of patients with stomach cancer (aAGP) are studied. Three fractions of AGP are divided into 3 groups according to their ability to bind to concanavalin A (ConA): AGP not binding to ConA (AGP-1) and AGP weakly (AGP-2) and strongly (AGP-3) binding to CortA. It is shown that native preparation of aAGP has a more potent inhibitory effect on lymphocyte proliferation than native preparation of nAGP. The most potent inhibitory effect is exerted by AGP-3. Native preparation of aAGP does not affect the secretion of intefleukin-2 (IL-2) by lymphocytes, whereas AGP-1 inhibits this process. The weakly bound fraction has a stimulatory effect both on the proliferative response and on IL-2 secretion.Key Words: orosomycoid; lymphocyte proliferation; interleukin-2 production al-Acid glycoprotein (orosomucoid) is an acute phase protein that may play an important role in the adaptation of the immune system to stress. Experimental data suggest that AGP is a naturally occurring immunomodulating agent which is present in blood serum in both health and pathology (neoplasms, rheumatoid arthritis, burn disease), and its blood level in the latter case may be 2-to 5-fold higher than normal [8,9,12]. There is evidence indicating that in some pathological processes an increase in the blood content of AGP is paralleled by structural changes in the hydrocarbon chains of this glycoprotein, which may affect its biological activity [8]. It has also been demonstrated that AGP with different degrees of glycosylation vary in the ability to inhibit the proliferation of cultured lymphocytes [6,11].Research Center for Medical Genetics, Russian Academy of Medical Sciences; Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow; Immunopreparat Conglomerate, UfaIn this study we attempted to investigate some mechanisms of the antiproliferative activity of various AGP forms that differ in degree of glycosylation. For this purpose we assessed in a wide dose range the ability of AGP preparations to inhibit the proliferation of lymphocytes and examined the effect of these preparations on the secretion of interleukin-2 (IL-2) by these ceUs. MATERIALS AND METHODSAGP was purified from the blood of healthy donors and from the ascitic fluid of patients with stomach cancer, as described elsewhere [1,5]. Fractionation by the glycosylation level was performed on a ConA-Sepharose column as described previously [4]. Three AGP fractions were obtained: not binding (AGP-1), weakly binding (AGP-2), and strongly binding (AGP-3) to CortA. The immunomodulating effects of these preparations were stud-0007-4888/94/0007-0755512.50 @1995 Plenum Publishing Corporation

We studied the effects of alpha1-acid glycoprotein on tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) production and lymphocyte response to phytohemagglutinin in cultured peripheral blood mononuclear leukocytes from 6 healthy donors. We observed 2 opposite responses to alpha1-acid glycoprotein: first, stimulation of TNF-alpha and IL-10 production and inhibition of lymphocyte proliferation, and second, suppression of cytokine production and stimulation of lymphocyte proliferation. In cell cultures isolated from 4 of 6 donors, the TNF-alpha/IL-10 ratio remained unchanged after addition of native alpha1-acid glycoprotein, but some fractions isolated by chromatography on concanavalin A-Sepharose changed this parameter. These changes were most pronounced after treatment with fraction C enriched with molecules with incomplete (biantennary) carbohydrate chains. The mechanisms of alpha1-acid glycoprotein-induced effects on peripheral blood mononuclear leukocytes are discussed.