Milligan C E, Webster L, Piros E T, Evans C J, Cunningham T J, Levitt P
Department of Zoology, University of Massachusetts, Amherst 01003, USA.
J Immunol. 1995 Jun 15;154(12):6571-81.
Macrophages have a prominent role in the injury response of the brain, yet the molecular mechanisms that control their invasion to the site of neuronal degeneration is unknown. After removal of the posterior cortex at birth, there is massive and specific targeting of nonresident macrophages to axotomized neurons in the lateral thalamus. The present study has identified an injury-induced, brain-derived chemotactic factor (BDCF) capable of eliciting chemotactic responses from resident peritoneal macrophages and brain macrophages. Conditioned media collected from tissue slices containing the axotomized central nervous system neurons exhibit BDCF activity. Initial experiments indicated that BDCF is a small peptide and, thus, we used specific pharmacologic reagents to characterize further BDCF activity. Naloxone, a pan opioid receptor antagonist, completely blocks BDCF activity. Although both kappa and mu opioid receptor antagonists failed to modify BDCF-induced macrophage chemotaxis, two specific delta receptor antagonists blocked BDCF. Analysis of BDCF by reverse phase HPLC and RIA revealed peak chemotactic activity in fractions consistent with the presence of an opioid peptide. The results suggest that cells in the brain respond to neuronal injury by producing and releasing opioids that can initiate a specific macrophage response.
巨噬细胞在大脑的损伤反应中发挥着重要作用，然而，控制其侵入神经元变性部位的分子机制尚不清楚。出生后切除后皮质后，非驻留巨噬细胞会大量且特异性地靶向外侧丘脑的轴突切断神经元。本研究发现了一种损伤诱导的脑源性趋化因子（BDCF），它能够引发驻留腹膜巨噬细胞和脑巨噬细胞的趋化反应。从含有轴突切断的中枢神经系统神经元的组织切片中收集的条件培养基具有BDCF活性。初步实验表明BDCF是一种小肽，因此，我们使用特定的药理试剂进一步表征BDCF活性。纳洛酮，一种泛阿片受体拮抗剂，完全阻断BDCF活性。虽然κ和μ阿片受体拮抗剂均未能改变BDCF诱导的巨噬细胞趋化性，但两种特异性δ受体拮抗剂可阻断BDCF。通过反相高效液相色谱法和放射免疫分析法对BDCF的分析显示，在与阿片肽存在一致的级分中存在峰值趋化活性。结果表明，大脑中的细胞通过产生和释放阿片类物质来响应神经元损伤，这些阿片类物质可以引发特定的巨噬细胞反应。
