Analysis of a murine nickel-allergy model promoted by endotoxin

2006年：我们发现，来自革兰氏阴性细菌的内毒素（或脂多糖，LPS）在致敏和诱发步骤中强烈促进镍（Ni）过敏，并且我们阐明了以下内容（发表于Clin Exp Allergy 2007;37：743-751）。Th 1型小鼠的炎症反应比Th 2型小鼠更严重. TNF或T细胞缺陷小鼠的炎症程度与对照小鼠相似，而IL-1缺陷小鼠和巨噬细胞耗竭小鼠的炎症程度明显较弱.组胺形成酶（HDC）活性随炎症进展而升高.肥大细胞缺陷小鼠的炎症倾向于增强，但在HPC缺陷小鼠中明显减弱。LPS还促进了对其他金属（Cr、Co、Pd、Cu和Ag）过敏的建立。2007年：我们发现以下内容（将在额外实验后提交）1.除巨噬细胞外，NK细胞和/或嗜碱性粒细胞可能参与镍过敏的发生。镍致敏小鼠对铬、钴、钯、铜、银也有反应.组胺参与了诱发过程.除LPS外，其他细菌成分或相关炎症物质（MDP、甘露聚糖、polyI：polyC或TLR 2配体、伴刀豆球蛋白A、含氮双膦酸盐）也在致敏和激发步骤中促进镍过敏。在引发步骤中，在LPS存在下，Ni在如此低的浓度如1 × 104 μ <-12>M（即，炎症可显著增强对金属过敏的敏感性）。

2006: We found that endotoxin from gram-negative bacteria (or lipopolysaccharide, LPS) strongly promotes nickel (Ni)-allergy in the steps of both sensitization and elicitation, and we clarified the followings (published in Clin Exp Allergy 2007;37:743-751).1. Inflammation was severer in Th1-dominant mice than in Th2-dominant mice.2. Extent of inflammation in mice deficient in TNF or T cells was similar to that in control mice, while it was markedly weak in IL-1-deficient mice and in macrophage-depleted mice.3. The activity of histamine-forming enzyme (HDC) increased in parallel with the progress of inflammation.4. Inflammation tended to be augmented in mast cell-deficient mice, but markedly weak in HDC-deficient mice.5. LPS also promoted the establishment of allergies to other metals (Cr, Co, Pd, Cu, and Ag).2007: We found the followings (will be submitted after additional experiments)1. In addition to macrophages, NK and/or basophiles may be involved in the development of Ni-allergy.2. Ni-sensitized mice responded to Cr, Co, Pd, Cu, and Ag, too.3. Histamine was involved in the process of elicitation.4. In addition to LPS, other bacterial constituents or related inflammatory substances (MDP, mannan, polyI:polyC, or TLR2 ligands, concanavalin A, nitrogen-containing bisphosphonates) also promoted Ni-allergy in the steps of both sensitization and elicitation.5. In the elicitation step, Ni, under the presence of LPS, induced inflammation at so low concentration as 1x10^<-12> M (i.e., inflammation may dramatically enhances the sensitivity to metal allergies).