Cauwels A, Frei K, Sansano S, Fearns C, Ulevitch R, Zimmerli W, Landmann R
Division of Infectious Diseases, Department of Research, University Hospitals, Basel, Switzerland.
J Immunol. 1999 Apr 15;162(8):4762-72.
Murine experimental meningitis models induced by either Escherichia coli LPS, live Streptococcus pneumoniae, or Listeria monocytogenes were used to study the origin and potential function of soluble CD14 (sCD14) in the brain during bacterial meningitis. Whereas intracerebral infection caused only a minor and/or transient increase of sCD14 levels in the serum, dramatically elevated concentrations of sCD14 were detected in the cerebrospinal fluid. Reverse-transcriptase PCR and FACS analysis of the leukocytes invading the subarachnoid compartment revealed an active amplification of CD14 transcription and concomitant surface expression. These findings were confirmed by in situ hybridization and immunohistochemical analysis. In contrast, parenchymal astrocytes and microglial cells were shown not to significantly contribute to the elevated levels of sCD14. Simultaneous intracerebral inoculation of rsCD14 and S. pneumoniae resulted in a markedly increased local cytokine response. Taken together, these data provide the first evidence that sCD14 can act as an inflammatory co-ligand in vivo. Thus, during bacterial meningitis, sCD14 is massively released by intrathecal leukocytes, and the sCD14 found in the cerebrospinal fluid can play an important role in the pathogenesis of this disease.
利用由大肠杆菌脂多糖、活的肺炎链球菌或单核细胞增生李斯特菌诱导的小鼠实验性脑膜炎模型，研究细菌性脑膜炎期间大脑中可溶性CD14（sCD14）的来源和潜在功能。虽然脑内感染仅导致血清中sCD14水平轻微和/或短暂升高，但在脑脊液中检测到sCD14浓度显著升高。对侵入蛛网膜下腔的白细胞进行逆转录聚合酶链反应和荧光激活细胞分选分析显示，CD14转录活跃扩增并伴随表面表达。这些发现通过原位杂交和免疫组织化学分析得到证实。相比之下，实质星形胶质细胞和小胶质细胞对sCD14水平升高的贡献不显著。同时脑内接种重组sCD14和肺炎链球菌导致局部细胞因子反应明显增强。综上所述，这些数据首次证明sCD14在体内可作为炎症共配体。因此，在细菌性脑膜炎期间，sCD14由鞘内白细胞大量释放，脑脊液中发现的sCD14在该疾病的发病机制中可能起重要作用。
