Elstad M R, Parker C J, Cowley F S, Wilcox L A, McIntyre T M, Prescott S M, Zimmerman G A
Department of Medicine, Veterans Affairs Medical Center, Salt Lake City, UT.
J Immunol. 1994 Jan 1;152(1):220-30.
We determined the mechanism by which opsonized zymosan particles, which are derived from yeast and composed of carbohydrate polymers, stimulate platelet-activating factor (PAF) synthesis by monocytes. A role for CD11b/CD18 was demonstrated because antibodies to this integrin decreased PAF synthesis, zymosan bearing only a ligand for CD11b/CD18 (iC3b) induced the synthesis of PAF, and monocytes that did not express CD11b/CD18 produced much less PAF than control monocytes. Ligation of CD11b/CD18 was not sufficient for PAF synthesis suggesting that an additional receptor was involved. Monocytes are known to bind beta-glucan which is a major component of zymosan. Opsonized beta-glucan particles stimulated the synthesis of PAF, and a soluble form of beta-glucan partially inhibited PAF synthesis in response to opsonized zymosan. Two lines of evidence suggested that the beta-glucan receptor mediating this response was distinct from CD11b/CD18. First, CD11b/CD18-deficient monocytes produced PAF when stimulated by zymosan opsonized with isolated C3b, a molecule that binds to complement receptor type 1 (CD35). Second, inducing contact of monocytes with zymosan by centrifugation resulted in PAF synthesis that was not inhibited by antibodies to CD11b/CD18. The combination of soluble beta-glucan and antibodies to CD11b/CD18 completely blocked PAF synthesis in response to opsonized zymosan. Together, these results demonstrate that induction of maximal PAF synthesis by serum-opsonized zymosan requires the concerted interactions of monocyte receptors for iC3b and beta-glucan. Additionally, they suggest that CD11b/CD18 facilitates binding of the particle and that a beta-glucan receptor transduces the activation signal.
我们确定了调理酵母聚糖颗粒刺激单核细胞合成血小板活化因子（PAF）的机制，酵母聚糖颗粒源自酵母，由碳水化合物聚合物组成。已证明CD11b/CD18发挥了作用，因为针对该整合素的抗体可降低PAF的合成，仅携带CD11b/CD18配体（iC3b）的酵母聚糖可诱导PAF的合成，且不表达CD11b/CD18的单核细胞产生的PAF比对照单核细胞少得多。CD11b/CD18的结合不足以合成PAF，这表明还涉及另一种受体。已知单核细胞可结合酵母聚糖的主要成分β-葡聚糖。调理后的β-葡聚糖颗粒刺激了PAF的合成，可溶性β-葡聚糖可部分抑制对调理酵母聚糖的PAF合成反应。有两条证据表明介导此反应的β-葡聚糖受体与CD11b/CD18不同。首先，用分离的C3b调理的酵母聚糖刺激CD11b/CD18缺陷型单核细胞时可产生PAF，C3b是一种与1型补体受体（CD35）结合的分子。其次，通过离心诱导单核细胞与酵母聚糖接触会导致PAF合成，而CD11b/CD18抗体并不能抑制这种合成。可溶性β-葡聚糖和CD11b/CD18抗体的组合完全阻断了对调理酵母聚糖的PAF合成反应。总之，这些结果表明，血清调理酵母聚糖诱导最大程度的PAF合成需要单核细胞iC3b和β-葡聚糖受体的协同相互作用。此外，这些结果还表明，CD11b/CD18促进颗粒的结合，而β-葡聚糖受体则转导激活信号。
