Kim Y S, Täuber M G
Infectious Diseases Laboratory, San Francisco General Hospital, California 94143, USA.
Infect Immun. 1996 Aug;64(8):3148-53. doi: 10.1128/iai.64.8.3148-3153.1996.
The present study examined the mechanism by which bacterial cell walls from two gram-positive meningeal pathogens, Streptococcus pneumoniae and the group B streptococcus, induced neuronal injury in primary cultures of rat brain cells. Cell walls from both organisms produced cellular injury to similar degrees in pure astrocyte cultures but not in pure neuronal cultures. Cell walls also induced nitric oxide production in cultures of astrocytes or microglia. When neurons were cultured together with astrocytes or microglia, the cell walls of both organisms became toxic to neurons. L-NAME, a nitric oxide synthase inhibitor, protected neurons from cell wall-induced toxicity in mixed cultures with glia, as did dexamethasone. In contrast, an excitatory amino acid antagonist (MK801) had no effect. Low concentrations of cell walls from either gram-positive pathogen added together with the excitatory amino acid glutamate resulted in synergistic neurotoxicity that was inhibited by L-NAME. The induction of nitric oxide production and neurotoxicity by cell walls was independent of the presence of serum, whereas endotoxin exhibited these effects only in the presence of serum. We conclude that gram-positive cell walls can cause toxicity in neurons by inducing the production of nitric oxide in astrocytes and microglia.
本研究考察了两种革兰氏阳性脑膜病原体——肺炎链球菌和B族链球菌的细菌细胞壁在大鼠脑细胞原代培养物中诱导神经元损伤的机制。两种病原体的细胞壁在纯星形胶质细胞培养物中产生的细胞损伤程度相似，但在纯神经元培养物中则不然。细胞壁还能诱导星形胶质细胞或小胶质细胞培养物中一氧化氮的产生。当神经元与星形胶质细胞或小胶质细胞共同培养时，两种病原体的细胞壁都会对神经元产生毒性。一氧化氮合酶抑制剂L-NAME与地塞米松一样，在与胶质细胞的混合培养物中能保护神经元免受细胞壁诱导的毒性。相比之下，兴奋性氨基酸拮抗剂（MK801）则没有效果。来自任何一种革兰氏阳性病原体的低浓度细胞壁与兴奋性氨基酸谷氨酸一起添加会导致协同神经毒性，L-NAME可抑制这种毒性。细胞壁诱导一氧化氮产生和神经毒性与血清的存在无关，而内毒素仅在有血清存在时才表现出这些作用。我们得出结论，革兰氏阳性细胞壁可通过诱导星形胶质细胞和小胶质细胞产生一氧化氮而对神经元造成毒性。
