ACTIVATION OF THE COMPLEMENT-SYSTEM BY (1-]3)-BETA-D-GLUCANS HAVING DIFFERENT DEGREES OF BRANCHING AND DIFFERENT ULTRASTRUCTURES

Activation of the alternative (APC) and classical (CPC) pathways of complement by fungal (1 --> 3)-beta-D-glucans having different degrees of branching (DB) and different conformations were examined by using human serum and plasma. The glucans used in this study were curdlan (no branch; 0/1), grifolan (one branch in every third main chain unit; 1/3), schizophyllan (1/3), SSG (1/2), and OL-2(2/3). Triple or single helix conformer of these glucans were prepared by heating at 150-degrees-C or dissolution in sodium hydroxide. Activation of APC by these glucans were dependent on incubation time, concentration, molecular weight, and DB. Interestingly, the triple helix conformer of all glucans tested activated APC stronger than a single helix one. The activity of branched glucans in plasma was weaker than those in serum. On the other hand, in the case of CPC, a single helix conformer activated CPC stronger than a triple helix one, and the activity was dependent on DB. Activation of CPC by a single helix conformer was thought to be dependent on the binding of beta-glucan to immunoglobulin in serum, because the complex was clearly detected by gel permeation chromatography only in the case of single helix one. From these results, it appears that the different conformers were recognized by the host complement systems in different ways. (1 --> 3)-beta-D-Glucan is one of the major constituents of fungal cell wall and is thought to be clearly recognized by the host immune systems. Conformation of these glucans in the cell wall was not determined in detail, but it is likely that both of the conformers are present in appropriate proportions in the cell wall. Considering these facts, recognition of glucans, dependent on the conformation, by both APC and CPC would be critically important in the host defense mechanisms.