Molecular biological approach to the treatment of endotoxin shock

内毒素(LPS)是一种有效的细胞生物反应调节剂，包括巨噬细胞、中性粒细胞和内皮细胞。内毒素的刺激是通过细胞表面受体CD14介导的。在我们的研究中，我们阐明了内毒素通过CD14与血清结合中性粒细胞，在与血清结合的条件下，内皮细胞上ICAM-1的表达也被增强。经肿瘤坏死因子-α或内毒素+血清处理后，中性粒细胞在EC单层上的黏附和产氧量明显增加。抗CD18的单抗可抑制中性粒细胞与EC的黏附和O2-的产生。抗CD11b单抗可抑制中性粒细胞的黏附，但可刺激O2的产生。提示CD11b介导的黏附为中性粒细胞产生超氧化物提供了信号(触发)。这些作用不能被抗肿瘤坏死因子抗体阻断。中性粒细胞产生的超氧化物在内毒素休克的发病机制中起着至关重要的作用。中性粒细胞的过度激发可能会给正常组织带来一定的毒性。在这个过程中，细胞凋亡可能为清除不需要的细胞提供了一种机制。GM-CSF和G-CSF在抗Fas抗体诱导人成熟中性粒细胞凋亡中的作用不同。GM-CSF可抑制细胞凋亡，保留中性粒细胞产生超氧化物的功能。据推测，GM-CSF是一种维持中性粒细胞存活的炎性细胞因子。白塞病是一种中性粒细胞功能明显增强的慢性疾病。己酮可可碱是一种膜流变剂，可调节受体介导的细胞功能。众所周知，己酮可可碱可以减轻中性粒细胞引起的组织损伤。我们检查了己酮可可碱在控制白塞病方面的效果，所有患者的临床状况和中性粒细胞功能都得到了改善。

Endotoxin (lipopolysaccharide ; LPS) is a potent biological response modifier of cells, including macrophages, neutrophils and endothelial cells (EC). LPS stimulation is mediated through a cell surface receptor, known as CD14. In our study, it is clarified that LPS primes neutrophils in the combination with serum via CD14 and the expression of ICAM-1 on EC is also enhanced under the condition with serum. The adhesion and O_2-production of neutrophils are markedly enhanced on the EC monolayr by treatment with TNF-alpha or LPS+serum. Monoclonal antibody (mAb) against CD18 inhibits neutrophil-EC adhesion and O_2-production. Anti-CD11b mAb inhibits adhesion, however, stimulates O_2-production These findings indicate that the adhesion mediated by CD11b provides the signal (trigger) for superoxide production by neutrophils. These effects are not blocked by anti-TNF antibody.Superoxide production by neutrophils plays a crucial role in the pathogenesis of endotoxin shock. The excessive priming of neutrophils may bring some toxicity to normal tissue. In the process, apoptosis may provide a mechanism for clearance of the unwanted cells. GM-CSF and G-CSF have different effects on the apoptosis of human mature neutrophils induced by anti-Fas antibody. GM-CSF suppress the apoptosis and retain neutrophil functions of superoxide production. It is postulated that GM-CSF works as an inflammatory cytokine which maintain neutrophil survival.Behcet disease is a chronic condition in which the functions of neutrophils are characteristically increased. Pentoxifylline is a membrane fluidizer that modulates receptor-mediated cellular functions. It is wellknown that pentoxifylline reduces neutrophil-induced tissue damage. We examined the effect of pentoxifylline in controlling Behcet disease and get improved clinical conditions and normalized neutrophil functions in all of our patients.