Molecular biological properties of lipidA derived from chronic inflammatory pathogens

幽门螺杆菌类脂A没有内毒素活性或内毒素活性很低，即对半乳糖胺负荷的小鼠的致死毒性，对兔的致热性，以及与大肠杆菌类型的合成类脂A(化合物506)相比的凝胶试验活性。幽门螺杆菌脂类A的内毒素性质也略弱于牙龈假单胞菌的低内毒素脂类A。幽门螺杆菌脂类A对小鼠脾单个核细胞的促有丝分裂活性也低于牙龈假单胞菌脂类A和化合物506。另一方面，幽门螺杆菌类脂A诱导人外周血单个核细胞(PBMC)产生白介素6(iIL-6)的能力与牙龈假单胞菌类脂A和化合物506相似。幽门螺杆菌脂类A对人自然杀伤细胞活性有一定的促进作用，对兔红细胞有较强的凝集作用。然而，幽门螺杆菌和牙龈假单胞菌的脂质AS在诱导人PBMC产生肿瘤坏死因子α(TNF-α)和诱导人牙龈成纤维细胞产生IL-8方面的活性低于化合物506。幽门螺杆菌脂蛋白A的结构特征可能与其具有较低的内毒素性质和较强的免疫生物学活性有关。此外，全身感染革兰氏阴性菌可导致感染性休克，其主要原因是内毒素内毒素(LPS)刺激巨噬细胞。在半乳糖胺负荷的小鼠肺泡巨噬细胞中，给予无毒的牙龈假单胞菌A脂可降低IL-1β的产生及其mRNA的表达，而与大肠杆菌内毒素合成的A脂A相比，A脂具有更高的钙调蛋白激酶活性。钙调蛋白激酶激活剂和抗IL-β的单抗也可以保护小鼠免受内毒素脂质A诱导的致命毒性。

Helicobacter pylori lipid A exhibited no or very low endotoxic activities i.e., lethal toxicity in galactosamine-loaded mice, pyrogenicity for rabbits and the activity of the Limulus test when compared with Escherichia coli-type synthetic lipid A (compound 506). The endotoxic properties of H.pylon lipid A were also a little weaker than those of the low endotoxic lipid A of P.gingivalis. The mitogenic activity of H.pylori lipid A in murine splenic mononuclear cells was also less than those of P.gingivalis lipid A and compound 506. On the other hand, H.pylori lipid A induced comparable production of interleukin-6 (IIL-6) by human peripheral blood mononuclear cells (PBMC) as compared with P.gingivalis lipid A and compound 506. H.pylori lipid A also increased definitely human natural killer cell activity, and strongly agglutinated rabbit erythrocytes. However, the lipid As of H.pylori and P.gingivalis showed lower activities in inducing tumor necrosis factor alpha (TNF-alpha) production by human PBMC and IL-8 production by human gingival fibroblasts than that of compound 506. The structural feature of H.pylori lipid A may be associated with low endotoxic properties and potent immunobiological activities. Futher, a systemic infection by Gram-negative bacteria results in septic shock which is mainly caused by macrophages stimulated with endotoxic lipopolysaccharides (LPS). The administration of non-toxic lipid A of P.gingivalis results in lower induction of IL-1beta production and its mRNA expression, whereas the lipid A exhibited higher calmodulin kinase activation in comparison with that of endotoxic synthetic lipid A of E.coli in alveolar macrophages of galactosamine-loaded mice. A calmodulin kinase activator and anti-IL-beta monoclonal antibody also protected mice against endotoxic lipid A-induced lethal toxicity.