The Acute Phase Response And The Implication Of Alpha1acid Glycoprotein

AGP has been implicated in depression as it is an endogenous inhibitor of platelet serotonin uptake and H3-imipramine binding (Abraham et al., 1987); it is also the important binding protein for many antidepressants (Kremer et al., 1988) and an inhibitor of human platelet aggregation (Costello et al., 1979). Specific alterations in glycosyla-tion of AGP occur in many pathophysiological states (Turner, 1992). These alterations are due to variations in the structure of the oligosaccharides present at a given site and have been referred to as the consequence of microheterogeneity. They accompany changes in the serum concentration of AGP, but are independent of its synthesis rate. The different glycophorms of serum AGP have varied immunoregulatory effects. Con-A-unreactive variants show significant (50-75%) inhibition of thymocyte proliferation (Pos et al., 1990), and they are also more effective in the induction of release of inter-leukin-1 inhibitor (Durand., 1989). These glycophorms also decrease polymorphonuclear neutrophil chemotaxis and oxidative metabolism (Vasson et al., 1994).

Changes in the serum concentrations of AGP result mainly from the effects of proinflammatory cytokines and other humoral factors upon their biosynthesis by the liver enzymes (Kushner and Mackiewicz, 1993). Changes in the proportions of different AGP glycophorms originate from modifications in the glycosylation mechanisms in the liver, mediated by a number of cytokines (IL-6, IL-1,TNF, interferon) and glucocorticoids (Van Dijk et al., 1994).

Crossed-affinity immunoelectrophoresis (CAIE) with free concanavalin A (Con A) as a ligand is the method to determinate different microheterogeneity glycophorms (Mackiewicz & Mackiewicz, 1986). CAIE reveals four microheterogeneity glycophorms (variants) of AGP: variant A—nonreactive with Con A, variant B—weakly reactive with Con A, variant C—reactive with Con A, and variant D—strongly reactive with Con A. A reactivity coefficient (RC) was calculated according to the formula: sum of

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