| Summary: | 碩士 === 國防醫學院 === 生物及解剖學研究所 === 91 === The incidence of septic shock caused by gram-positive bacteria has been increasing over the past two decades. Currently, between one-third and one-half of all cases of sepsis are caused by gram-positive microorganisms. Lipoteichoic acid (LTA), a cell wall component from gram-positive bacterium (Staphylococcus aureus), could also induce encephalomyelitis and meningeal inflammation. LTA enhanced the production of nitric oxide (NO) through expression of iNOS in murine macrophages. Whether microglia can also be activated by the sole cell wall product of gram-positive bacteria, LTA, is unclear！
In the present study, we found that LTA significantly changed external morphology of isolated microglia and caused cell death at high concentration. LTA of low doses also enhanced microglial proliferation. MHC class II antigens and the potential receptors for LTA such as the complement type 3 (CR3), CD14 and macrophage scavenger receptors (SR) on microglia were also augmented after LTA treatment. The latter further induced NO release and inducible nitric oxide synthase (iNOS) expression. LTA-induced NO accumulation was detected as early as at 2 h in microglial culture and significantly attenuated by the pretreatment with anti-CD14, CR3 or SR antibody. LTA activated phosphorylated p38, ERK or JNK in cultured microglia. NO production also drastically decreased by SB203580 (p38 inhibitor) or pyrrolidine dithiocarbanate (an inhibitor of nuclear factor κB), indicating that p38 and NFκB were involved in microglial NO release after LTA challenge. These results suggest that gram-positive bacterial product such as LTA can activate microglia to release NO via the signal transduction pathway involving in LTA receptors (e.g. CD14, CR3 or SR), p38 and NFκB.
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