Constitutive expression of CXCL2/MIP-2 is restricted to a Gr-1high, CD11b+, CD62Lhigh subset of bone marrow derived granulocytes

Constitutive expression of CXCL2/MIP-2 is restricted to a Gr-1high, CD11b+, CD62Lhigh subset of bone marrow derived granulocytes
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DOI:
10.1093/intimm/dxh169
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发表时间:
2004-11-01
影响因子:
4.4
通讯作者:
Beuscher, HU
Beuscher, HU
中科院分区:
医学3区
文献类型:
--
作者:
Matzer, SP;Rödel, F;Beuscher, HU

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CXCL2/巨噬细胞炎症蛋白(MIP)-2是一种可诱导的小鼠趋化因子,参与了多形核粒细胞对感染部位的吸引。相比之下,它在小鼠体内作为结构性产生的趋化因子的作用尚不清楚。本研究旨在明确CXCL2/MIP-2的细胞来源,并与其他趋化因子在正常小鼠外周淋巴组织和骨髓中的表达模式进行比较。结果表明,CXCL2/MIP-2mRNA的结构性表达仅限于骨髓。RT-PCR和FACS分析显示,CXCL2/MIP-2的产生仅限于骨髓来源的Gr-1(高)粒细胞的一个特殊亚群。该亚群表面表达CD11b(+)、CD62L(高)和CXCR2(+),占骨髓细胞总数的4~6%。BM细胞体外刺激不能增加CXCL2/MIP-2(+)粒细胞的数量。细胞内CXCL2/MIP-2与其受体的表面表达没有严格的相关性,因为大多数CXCR2(+)/Gr-1(高)细胞缺乏CXCL2/MIP-2染色。在对照组中,未检测到CXCL1/KC在骨髓中的表达,但在缺乏CXCL2/MIP-2的情况下,在外周组织中发现了CXCL1/KC的表达。总之,我们的结果表明,CXCL2/MIP-2和CXCL1/KC在正常小鼠中以组织特异性的方式表达,CXCL2/MIP-2在定义明确的CD11b(+)、CD62L(高)、Gr-1(高)粒细胞亚群中产生,从而为这两种趋化因子的独立调控提供了可能的解释。
CXCL2/macrophage inflammatory protein (MIP)-2 is an inducible murine chemokine involved in attraction of polymorphonuclear granulocytes to sites of infection. In comparison, its role as constitutive produced chemokine in mice is unclear. The present study aimed to specify the cellular source of constitutively produced CXCL2/MIP-2 and to examine its expression pattern in comparison to other chemokines in peripheral lymphoid tissues as well as bone marrow (BM) of normal mice. The results showed that constitutive expression of CXCL2/MIP-2 mRNA was restricted to BM. As revealed by RT-PCR and FACS analysis, CXCL2/MIP-2 production was restricted to a specialized subset of BM derived Gr-1(high) granulocytes. This subset was characterized by surface expression of CD11b(+), CD62L(high) and CXCR2(+) and accounted for 4-6% of total BM cells. In vitro stimulation of BM cells did not increase the number of CXCL2/MIP-2(+) granulocytes. Intracellular CXCL2/MIP-2 was not strictly correlated to surface expression of its receptor, as the majority of the CXCR2(+)/Gr-1(high) cells lacked CXCL2/MIP-2 staining. In controls, CXCL1/KC expression was not detected in BM but was found in peripheral tissues in the absence of CXCL2/MIP-2. Together, our results show that CXCL2/MIP-2 and CXCL1/KC are differentially expressed in a tissue specific manner in normal mice and that CXCL2/MIP-2 is produced in a well-defined CD11b(+), CD62L(high), Gr-1(high) subset of BM granulocytes, thereby providing a possible explanation for the independent regulation of both chemokines.