Czop J K, Valiante N M, Janusz M J
Department of Medicine, Harvard Medical School, Boston, Massachusetts.
Prog Clin Biol Res. 1989;297:287-96.
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.
在没有调理素的情况下，人类单核细胞通过β-葡聚糖受体吞噬替代补体途径的颗粒激活剂。单核细胞对可溶性β-葡聚糖的识别选择性地抑制颗粒激活剂的摄取，并且对由单核细胞Fc-IgG、补体或纤连蛋白受体介导的反应没有影响。单核细胞β-葡聚糖受体识别的最小配体单位是存在于酵母细胞壁中的耐酸七葡糖苷。已制备出小鼠单克隆抗β-葡聚糖抗体，其中一种可完全中和经高效液相色谱纯化的七葡糖苷的抑制能力。该抗体已被用作制备抗独特型抗体的免疫原。用低浓度抗独特型抗体预处理单核细胞可抑制单核细胞对酵母聚糖颗粒的摄取，但不抑制对EsIgG的摄取，这表明该抗体对单核细胞β-葡聚糖受体具有特异性，是进一步进行受体研究的有力探针。单核吞噬细胞上还存在其他对碳水化合物具有特异性的受体。甘露糖/岩藻糖受体和半乳糖受体已被分离和克隆。诸如活性七葡糖苷的结构类似物和抗独特型抗体等探针的开发，将使β-葡聚糖受体达到类似的明确阶段。给β-葡聚糖受体研究增加相当大难度且其他碳水化合物受体不存在的一个主要因素是，需要由几个葡萄糖单元排列提供的结构构象，而不是识别例如糖缀合物中的己糖残基。将这些受体命名为β-葡聚糖受体不经意间把我们带入了非免疫防御的新领域。动物研究表明，具有1,3-和/或1,6-连接的β-葡聚糖是活性药物制剂，可迅速赋予正常宿主对多种生物损伤的保护作用。β-葡聚糖受体提供了一种启动宿主反应性增强状态的机制。
