Hyaluronan (HA) fragments induce chemokine gene expression in alveolar macrophages - The role of HA size and CD44
Hyaluronan (HA) fragments induce chemokine gene expression in alveolar macrophages - The role of HA size and CD44
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DOI：
10.1172/jci119054
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发表时间：
1996-11-15
影响因子：
15.9
通讯作者：
Noble, PW
中科院分区：
文献类型：
--
作者：
McKee, CM;Penno, MB;Noble, PW
透明质酸（HA）是细胞外基质的糖胺聚糖成分，在其天然形式中HA作为高分子量聚合物存在，但在炎症期间较低分子量片段积累。我们已经鉴定了由HA片段而不是由高分子量HA在巨噬细胞中诱导的炎性基因的集合，这些包括趋化因子基因家族的几个成员：巨噬细胞炎性蛋白-1 α、巨噬细胞炎性蛋白-1 β、细胞因子应答基因-2、单核细胞趋化蛋白-1，并调节活化，正常T细胞表达和分泌，小至六聚体的HA片段能够在小鼠肺泡巨噬细胞系中诱导这些基因的表达，并且HA受体CD 44的单克隆抗体完全阻断荧光素标记的HA与这些细胞的结合并显著抑制HA诱导的基因表达。我们还研究了HA片段诱导特发性肺纤维化患者的人肺泡巨噬细胞中趋化因子基因表达的能力，发现白细胞介素-8 mRNA被显著诱导。这些数据支持了炎症过程中产生的HA片段诱导巨噬细胞基因表达的假设，这些基因在炎症反应的发展和维持中是重要的。
Hyaluronan (HA) is a glycosaminoglycan constituent of extracellular matrix, In its native form HA exists as a high molecular weight polymer, but during inflammation lower molecular weight fragments accumulate. We have identified a collection of inflammatory genes induced in macrophages by HA fragments but not by high molecular weight HA, These include several members of the chemokine gene family: macrophage inflammatory protein-1 alpha, macrophage inflammatory protein-1 beta, cytokine responsive gene-2, monocyte chemoattractant protein-1, and regulated on activation, normal T cell expressed and secreted, HA fragments as small as hexamers are capable of inducing expression of these genes in a mouse alveolar macrophage cell line, and monoclonal antibody to the HA receptor CD44 completely blocks binding of fluorescein-labeled HA to these cells and significantly inhibits HA-induced gene expression. We also investigated the ability of HA fragments to induce chemokine gene expression in human alveolar macrophages from patients with idiopathic pulmonary fibrosis and found that interleukin-8 mRNA is markedly induced, These data support the hypothesis that HA fragments generated during inflammation induce the expression of macrophage genes which are important in the development and maintenance of the inflammatory response.