Constitutive expression of macrophage-inflammatory protein 2 (MIP-2) mRNA in bone marrow gives rise to peripheral neutrophils with preformed MIP-2 protein
Constitutive expression of macrophage-inflammatory protein 2 (MIP-2) mRNA in bone marrow gives rise to peripheral neutrophils with preformed MIP-2 protein
复制标题
DOI：
10.4049/jimmunol.167.8.4635
复制
发表时间：
2001-10-15
影响因子：
4.4
通讯作者：
Beuscher, HU
中科院分区：
文献类型：
--
作者：
Matzer, SP;Baumann, T;Beuscher, HU
巨噬细胞炎症蛋白2 （MIP-2）是一种主要的CXC趋化因子，参与多形核中性粒细胞（pmn）向炎症部位的迁移。虽然细胞培养实验已经确定了不同类型的细胞可以产生MIP-2，但体内的细胞来源尚未明确。本研究通过免疫组织化学染色和趋化因子mRNA表达分析，旨在定位正常小鼠和小肠结肠炎耶尔森菌攻毒小鼠组织中产生MIP-2的细胞。结果显示MIP-2 mRNA在正常小鼠骨髓（BM）中有组成性表达，而在其他器官如脾、肺或肝脏中没有表达。MIP-2蛋白在所有被检测的器官中都被发现，但它只与细胞表面标记物gr - 1染色阳性的PMNs相关。细菌感染引起脾脏MIP-2阳性PMNs数量增加5倍，同时脾脏MIP-2 mRNA水平明显升高。这与BM中产生mip -2细胞的3倍损失密切相关。由于TNF刺激后PMNs中MIP-2 mRNA表达增加，结果表明新招募的PMNs可以通过TNF刺激的转录补充其MIP-2含量。综上所述，这些数据暗示了BM中pmn的一部分组成性产生MIP-2，并论证了MIP-2通过其在循环pmn中的储存而快速动员的可能性。
Macrophage-inflammatory protein 2 (MIP-2) is a major CXC chemokine involved in the migration of polymorphonuclear neutrophils (PMNs) to sites of inflammation. Although cell culture experiments have identified different cell types that can produce MIP-2, the cellular sources in vivo are not clearly defined. By using immunohistochemical staining and analysis of chemokine mRNA expression, the present study aimed to localize cells producing MIP-2 in tissues of normal mice and mice challenged with Yersinia enterocolitica. The results showed a constitutive expression of MIP-2 mRNA in bone marrow (BM) of normal mice, but not in other organs such as spleen, lung, or liver. MIP-2 protein was found in all organs tested but it was exclusively associated with PMNs that stained positive with the cell surface marker Gr-l. Bacterial infection caused a 5-fold increase in the number of MIP-2-positive PMNs recruited to spleens concomitant with a strong increase of splenic MIP-2 mRNA. This correlated well with a 3-fold loss of MIP-2-producing cells in BM. Because MIP-2 mRNA expression in PMNs was increased after stimulation with TNF, the results indicate that newly recruited PMNs can supplement their MIP-2 content through TNF-stimulated transcription. Together, the data imply a constitutive production of MIP-2 by a subset of PMNs in BM and argue for the possibility of a rapid mobilization of MIP-2 through its storage in circulating PMNs.