Analysis of reactive oxygen species, NO, CO and H_2S as therapeutic targets in the immune complex diseases

为了研究H_2S在IC诱导疾病中的作用，我们以NaHS为H_2S供体进行了反向被动皮肤Arthus反应。此外，我们用选择素缺陷（选择素^<-/->）小鼠进行了类似的实验，以确定选择素分子在H_2S介导途径中的作用。外源性应用H_2S可显著减轻野生型（WT）小鼠与Arthus反应相关的炎症反应。即，与未处理的WT小鼠相比，NaHS处理的WT小鼠病变皮肤中肿瘤坏死因子-α、干扰素-γ mRNA表达量和中性粒细胞数量显著降低。NaHS处理显著降低了E-和p -选择素^<-/->小鼠病变皮肤的这三个参数，但对L-选择素^<-/->小鼠无显著影响。在对WT小鼠注射E-、P-和l -选择素单克隆抗体的阻断研究中获得了非常相似的结果。我们的研究结果表明，外源性应用H_2S通过l -选择素参与的途径，而不是通过E或p -选择素参与的途径，减轻了反向被动Arthus反应中的炎症反应。

To assess the roles of H_2S in the IC induced diseases, reverse passive cutaneous Arthus reaction was conducted using NaHS as an H_2S donor. Furthermore, we conducted similar experiments using selectin-deficient (selectin^<-/->) mice to determine the involvement of selectin molecules in the H_2S mediated pathway. Exogenous application of H_2S dramatically attenuated inflammatory reactions in wild type (WT) mice associated with Arthus reaction. Namely, mRNA expressions of tumor necrosis factor-α, interferon-γ and neutrophil numbers were significantly reduced in the lesional skins of NaHS treated WT mice relative to untreated ones. NaHS treatment significantly reduced these three parameters in the lesional skins of E- and P-selectin^<-/-> mice, but not in those of L- selectin^<-/-> mice. Quite similar results were obtained in the blocking study using WT mice injected with monoclonal antibodies to E-, P- and L-selectin. Our results indicated that exogenous application of H_2S attenuates inflammatory responses in reverse passive Arthus reaction through L-selectin involved pathways, but not through E- or P-selectin pathways.