Stein M, Keshav S, Harris N, Gordon S
Sir William Dunn School of Pathology, Oxford, United Kingdom.
J Exp Med. 1992 Jul 1;176(1):287-92. doi: 10.1084/jem.176.1.287.
Expression of the macrophage mannose receptor is inhibited by interferon gamma (IFN-gamma), a T helper type 1 (Th-1)-derived lymphokine. Interleukin 4 (IL-4), a Th-2 lymphocyte product, upregulates major histocompatibility class II antigen expression but inhibits inflammatory cytokine production by macrophages. We have studied the effect of IL-4 on expression of the macrophage mannose receptor (MMR) by elicited peritoneal macrophages. We found that recombinant murine IL-4 enhances MMR surface expression (10-fold) and activity (15-fold), as measured by the respective binding and degradation of 125I-mannose-bovine serum albumin. Polymerase chain reaction analysis of cDNAs from purified primary macrophage populations revealed that MMR, but not lysozyme or tumor necrosis factor alpha, mRNA levels were markedly increased by IL-4. The above effects were associated with morphologic changes. These data establish IL-4 as a potent and selective enhancer of murine MMR activity in vitro. IL-4 induces inflammatory macrophages to adopt an alternative activation phenotype, distinct from that induced by IFN-gamma, characterized by a high capacity for endocytic clearance of mannosylated ligands, enhanced (albeit restricted) MHC class II antigen expression, and reduced proinflammatory cytokine secretion.
巨噬细胞甘露糖受体的表达受到干扰素γ（IFN-γ）的抑制，IFN-γ是一种1型辅助性T细胞（Th-1）衍生的淋巴因子。白细胞介素4（IL-4）是Th-2淋巴细胞的产物，它能上调主要组织相容性复合体II类抗原的表达，但会抑制巨噬细胞产生炎性细胞因子。我们研究了IL-4对诱导性腹膜巨噬细胞中巨噬细胞甘露糖受体（MMR）表达的影响。我们发现，重组鼠IL-4可增强MMR的表面表达（10倍）和活性（15倍），这是通过125I-甘露糖-牛血清白蛋白的各自结合和降解来测定的。对纯化的原代巨噬细胞群体的cDNA进行聚合酶链反应分析表明，IL-4可使MMR的mRNA水平显著增加，但溶菌酶或肿瘤坏死因子α的mRNA水平则无明显变化。上述效应与形态学变化有关。这些数据表明，IL-4在体外是鼠MMR活性的一种强效且选择性的增强剂。IL-4可诱导炎性巨噬细胞呈现一种不同于IFN-γ诱导的替代激活表型，其特征是对甘露糖基化配体的内吞清除能力强、MHC II类抗原表达增强（尽管有限）以及促炎细胞因子分泌减少。
