Neutrophil chemoattractant genes KC and MIP-2 are expressed in different cell populations at sites of surgical injury
Neutrophil chemoattractant genes KC and MIP-2 are expressed in different cell populations at sites of surgical injury
复制标题
DOI：
10.1189/jlb.0803370
复制
发表时间：
2004-04-01
影响因子：
5.5
通讯作者：
Hamilton, TA
中科院分区：
文献类型：
--
作者：
Armstrong, DA;Major, JA;Hamilton, TA
KC和巨噬细胞炎性蛋白-2（MIP-2）是CXC趋化因子，在手术损伤后的皮肤中表现出不同的时间表达模式。原位杂交分析表明，这两种趋化因子表达的不同类型的细胞在不同的时间损伤后。皮肤成纤维细胞和内皮细胞主要负责手术后皮肤中的KC表达。相比之下，MIP-2的产生似乎仅限于浸润性炎性白细胞，包括中性粒细胞和单核细胞，它们在反应后期出现。使用分离的原代和长期培养的细胞类型在体外重现了这种细胞类型特异性的趋化因子表达模式。原代真皮成纤维细胞用白细胞介素-1 α刺激后主要表达KC，而MIP-2表达很少，腹膜渗出液中性粒细胞在体外刺激后产生与KC一样多或更多的MIP-2。虽然外源刺激的集合可以诱导KC和MIP-2的表达，但表达的定量比率反映了细胞类型而不是刺激。KC在内皮细胞中的选择性表达超过MIP-2，这是由于KC基因转录显著增加，而不是由于mRNA衰减速率的改变。这些结果表明，不同的CXC趋化因子在髓细胞与非髓细胞类型中显示出有限的表达，并且体内炎症部位的趋化因子表达模式反映了这些不同细胞类型的时序贡献。
KC and macropbage-inflammatory protein-2 (MIP-2) are CXC chemokines that exhibit distinct temporal patterns of expression in the skin following surgical injury. In situ hybridization analysis demonstrates that these two chemokines are expressed by distinct cell types at different times following injury. Dermal fibroblasts and endothelial cells are primarily responsible for KC expression in the skin 6 It following surgery. In contrast, MIP-2 production appears to be restricted to infiltrating inflammatory leukocytes including neutrophils and monocytes, which appear later in the response. This cell type-specific pattern of chemokine expression is recapitulated in vitro using isolated primary- and long-term-cultured cell types. Primary dermal fibroblasts stimulated with interleukin-1alpha express predominantly KC and very little MIP-2, and peritoneal exudate neutrophils produce as much or more MIP-2 as KC following stimulation in vitro. Although a collection of exogenous stimuli can induce expression of KC and MIP-2, the quantitative ratio for expression reflects the cell type and not the stimulus. The selective expression of KC over MIP-2 in endothelial cells results from markedly greater KC gene transcription and not from alterations in the rate of mRNA decay. These results demonstrate that distinct CXC chemokines show restricted expression in myeloid versus nonmyeloid cell types and that patterns of chemokine expression at sites of inflammation in vivo reflect the temporally ordered contribution of these distinct cell types.