Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation.
Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation.
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DOI：
10.1084/jem.176.1.287
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发表时间：
1992-07-01
期刊：
影响因子：
--
通讯作者：
Gordon S
中科院分区：
文献类型：
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作者：
Stein M;Keshav S;Harris N;Gordon S
巨噬细胞甘露糖受体的表达被干扰素γ（IFN-γ）抑制，干扰素γ是一种辅助性T细胞1型（Th-1）衍生的淋巴因子。白细胞介素4（IL-4），Th-2淋巴细胞的产物，上调主要组织相容性II类抗原的表达，但抑制巨噬细胞的炎性细胞因子的产生。我们研究了IL-4对巨噬细胞甘露糖受体（MMR）表达的影响。我们发现，重组鼠IL-4增强MMR表面表达（10倍）和活性（15倍），分别通过125 I-甘露糖-牛血清白蛋白的结合和降解。从纯化的原代巨噬细胞群体的cDNA的聚合酶链反应分析显示，MMR，但不是溶菌酶或肿瘤坏死因子α，mRNA水平显着增加IL-4。上述作用与形态学变化有关。这些数据确立了IL-4作为体外小鼠MMR活性的有效和选择性增强剂。IL-4诱导炎性巨噬细胞采用不同于IFN-γ诱导的活化表型的替代活化表型，其特征在于内吞清除甘露糖基化配体的高能力、增强的（尽管受限的）MHC II类抗原表达和减少的促炎性细胞因子分泌。
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.