Phagocytosis of particulate activators of the human alternative complement pathway through monocyte beta-glucan receptors.

Human monocytes phagocytose particulate activators of the alternative complement pathway through beta-glucan receptors in the absence of opsonins. Recognition of soluble beta-glucans by monocytes selectively inhibits ingestion of particulate activators and has no effect on responses mediated by monocyte receptors for Fc-IgG, complement, or fibronectin. The smallest ligand unit recognized by monocyte beta-glucan receptors is an acid-resistant heptaglucoside present in yeast cell walls. Mouse monoclonal anti-beta-glucan antibodies have been prepared, one of which completely neutralizes the inhibitory capacity of the HPLC-purified heptaglucoside. This antibody has been used as immunogen for the preparation of an anti-Id. The pretreatment of monocytes with low concentrations of anti-Id inhibits monocyte ingestion of zymosan particles but not EsIgG, suggesting that this antibody has specificity for monocyte beta-glucan receptors and is a powerful probe for further receptor studies. Other receptors with specificities for carbohydrates are also present on mononuclear phagocytes. Receptors for mannose/fucose and those for galactose have been isolated and cloned. The development of probes, such as structural analogs of the active heptaglucoside and the anti-Id, will bring the beta-glucan receptors to a similar stage of definition. A major factor that adds a considerable degree of difficulty to studies of the beta-glucan receptors and is not shared by the other receptors for carbohydrates is the requirement for structural conformations provided by the alignment of several glucose units rather than the recognition of a hexose residue in, for example, a glycoconjugate. The designation of these receptors as beta-glucan receptors has inadvertently taken us into a new area of nonimmune defense. Animal studies indicate that beta-glucans with 1,3- and/or 1,6-linkages are active pharmacologic agents that rapidly confer protection to a normal host against a variety of biologic insults. The beta-glucan receptors provide a mechanism by which a heightened state of host responsiveness is initiated.