Neutralization of macrophage inflammatory protein 2 (MIP-2) and MIP-1α attenuates neutrophil recruitment in the central nervous system during experimental bacterial meningitis
Neutralization of macrophage inflammatory protein 2 (MIP-2) and MIP-1α attenuates neutrophil recruitment in the central nervous system during experimental bacterial meningitis
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DOI：
10.1128/iai.67.5.2590-2601.1999
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发表时间：
1999-05-01
影响因子：
3.1
通讯作者：
Link, H
中科院分区：
文献类型：
--
作者：
Diab, A;Abdalla, H;Link, H
趋化因子是低分子量的趋化性细胞因子，已表明在血管周围白细胞特定亚群的迁移以及在组织损伤部位的聚集过程中发挥核心作用。我们利用原位杂交（ISH）研究了巨噬细胞炎性蛋白2（MIP - 2）、MIP - 1α、单核细胞趋化蛋白1（MCP - 1）和RANTES的mRNA诱导情况。给幼鼠腹腔注射b型流感嗜血杆菌攻击其大脑后，导致MIP - 2、MIP - 1α、MCP - 1和RANTES呈时间依赖性表达，在接种后24至48小时达到最大值。免疫组织化学显示，浸润脑膜、脑室系统和脑室周围区域的中性粒细胞和巨噬细胞显著增加。MIP - 2、MIP - 1α、MCP - 1和RANTES mRNA表达的动力学与炎症细胞的募集以及疾病的严重程度平行。给予抗MIP - 2或抗MIP - 1α抗体导致中性粒细胞显著减少。给予抗MCP - 1抗体显著降低巨噬细胞的浸润。ISH和免疫组织化学的联合研究表明，MIP - 2和MIP - 1α阳性细胞为中性粒细胞和巨噬细胞，MCP - 1阳性细胞为中性粒细胞、巨噬细胞和星形胶质细胞，RANTES的表达主要定位于常驻星形胶质细胞和小胶质细胞。本研究表明，在体内阻断MIP - 2或MIP - 1α的生物活性会导致中性粒细胞流入减少。这些数据也首次证明C - C趋化因子MIP - 1α在体内参与中性粒细胞的募集。
Chemokines are low-molecular-weight chemotactic cytokines that have been shown to play a central role in the perivascular transmigration and accumulation of specific subsets of leukocytes at sites of tissue damage. Using in situ hybridization (ISH), we investigated the mRNA induction of macrophage inflammatory protein 2 (MIP-2), MIP-1 alpha, monocyte chemoattractant protein 1 (MCP-1), and RANTES. Challenge of infant rats' brains with Haemwophilus influenzae type b intraperitoneally resulted in the time-dependent expression of MIP-2, MIP-1 alpha, MCP-1, and RANTES, which was maximal 24 to 48 h postinoculation. Immunohistochemistry showed significant increases in neutrophils and macrophages infiltrating the meninges, the ventricular system, and the periventricular area. The kinetics of MIP-2, MIP-1 alpha, MCP-1, and RANTES mRNA expression paralleled those of the recruitment of inflammatory cells and disease severity. Administration of anti-MIP-2 or anti-MIP-1 alpha antibodies (Abs) resulted in significant reduction of neutrophils. Administration of anti-MCP-1 Abs significantly decreased macrophage infiltration. Combined studies of ISH and immunohistochemistry showed that MIP-2- and MIP-1 alpha positive cells were neutrophils and macrophages, MCP 1-positive cells were neutrophils, macrophages, and astrocytes, Expression of RANTES was localized predominantly to resident astrocytes and microglia, The present study indicates that blacking of MIP-2 or MIP-1 alpha bioactivity in vivo results in decreased neutrophil influx, These data are also the first demonstration that the C-C chemokine MIP-1 alpha is involved in neutrophil recruitment in vive.