Waytes A T, Malbran A, Bobak D A, Fries L F
Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
J Immunol. 1991 Apr 15;146(8):2694-700.
Opsonization of the C3b receptor (CR1) on phagocytic cells with C3b enhances both attachment of targets to the cells and subsequent IgG-dependent ingestion of these targets. To explore mechanisms involved in this increased phagocytosis, we adhered cultured human monocytes to surfaces pre-coated with CR1 ligand or control proteins and quantitated ingestion of sheep E opsonized with IgG alone. Three ligands for CR1 resulted in markedly enhanced phagocytosis of targets when compared individually to a panel of non-ligands, as determined by both the proportion of monocytes ingesting targets (percent phagocytosis) and by the number of targets ingested per 100 monocytes (phagocytic index). The ligands included purified C3b, iC3, and Fab fragments of 1B4, a monoclonal anti-CR1, which resulted in a percent phagocytosis of 56.3 (p less than 0.01), 59.0 (p less than 0.01), and 54.4 (p less than 0.02) and a phagocytic index of 281.2 (p less than 0.01), 281.1 (p less than 0.01), and 247.1 (p less than 0.02), respectively. Control proteins including human serum albumin, hemoglobin, Fab fragments of anti-fibronectin, anti-beta 2 microglobulin, and MOPC 21, and Fc fragments of 1B4 and MOPC 21 produced no significant stimulation of phagocytosis, nor did F(ab')2 fragments of monoclonal anti-CR3, M1/70. CR1-specific augmentation of target ingestion was apparent with monocytes cultured in serum-free medium for 1 to 7 days, but was not seen with freshly elutriated cells. Phagocytosis of unopsonized or IgM-coated targets was minimal. These results suggest that the adherent monocytes are primed by CR1 cross-linking for enhanced FcR-mediated phagocytosis even when the CR1 ligand is not present on the targets. This contrasts with the behavior of CR3, and demonstrated functional divergence between these C3 fragment receptors in the phagocytic process.
吞噬细胞上的C3b受体（CR1）被C3b调理后，会增强靶标与细胞的附着以及随后IgG依赖的对这些靶标的摄取。为了探究这种吞噬作用增强所涉及的机制，我们将培养的人单核细胞黏附到预先包被有CR1配体或对照蛋白的表面，并对仅用IgG调理的绵羊红细胞的摄取进行定量。与一组非配体相比，当单独测定时，三种CR1配体导致靶标的吞噬作用显著增强，这通过摄取靶标的单核细胞比例（吞噬百分比）和每100个单核细胞摄取的靶标数量（吞噬指数）来确定。这些配体包括纯化的C3b、iC3以及单克隆抗CR1抗体1B4的Fab片段，其吞噬百分比分别为56.3（p<0.01）、59.0（p<0.01）和54.4（p<0.02），吞噬指数分别为281.2（p<0.01）、281.1（p<0.01）和247.1（p<0.02）。对照蛋白包括人血清白蛋白、血红蛋白、抗纤连蛋白的Fab片段、抗β2微球蛋白和MOPC 21，以及1B4和MOPC 21的Fc片段，均未产生对吞噬作用的显著刺激，单克隆抗CR3抗体M1/70的F(ab')2片段也未产生刺激作用。在无血清培养基中培养1至7天的单核细胞中，CR1特异性增强靶标摄取的现象明显，但在新鲜淘洗的细胞中未观察到。未调理或IgM包被的靶标的吞噬作用极小。这些结果表明，即使靶标上不存在CR1配体，黏附的单核细胞也会因CR1交联而被致敏，从而增强FcR介导的吞噬作用。这与CR3的行为形成对比，并证明了这些C3片段受体在吞噬过程中的功能差异。
