Transformation of circulating leukocytes from a dormant into an activated state with changing rheological properties leads to a major shift of their behavior in the microcirculation. Low levels of pseudopod formation or expression of adhesion molecules facilitate relatively free passage through microvessels while activated leukocytes with pseudopods and enhanced levels of adhesion membrane proteins become trapped in microvessels, attach to the endothelium and migrate into the tissue. The transformation of leukocytes into an activated state is seen in many diseases. While mechanisms for activation due to infections, tissue trauma, as well as non-physiological biochemical or biophysical exposures are well recognized, the mechanisms for activation in many diseases have not been conclusively liked to these traditional mechanisms and remain unknown. We summarize our recent evidence suggesting a major and surprising role of digestive enzymes in the small intestine as root causes for leukocyte activation and microvascular disturbances. During normal digestion of food digestive enzymes are compartmentalized in the lumen of the intestine by the mucosal epithelial barrier. When permeability of this barrier increases, these powerful degrading enzymes leak into the wall of the intestine and into the systemic circulation. Leakage of digestive enzymes occurs for example in physiological shock and multi-organ failure. Entry of digestive enzymes into the wall of the small intestine leads to degradation of the intestinal tissue in an autodigestion process. The digestive enzymes and tissue/food fragments generate not only activate leukocytes but also cause numerous cell dysfunctions. For example, proteolytic destruction of membrane receptors, plasma proteins and other biomolecules occurs. We conclude that escape of digestive enzymes from the intestinal track serves as a major source of cell dysfunction, morbidity and even mortality, including abnormal leukocyte activation seen in rheological studies.

中文翻译：

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自消化假说：流变和心血管细胞功能障碍中蛋白水解受体的裂解1。

流变性质不断变化的循环白细胞从休眠状态转变为活化状态会导致其在微循环中的行为发生重大变化。伪足的低水平形成或粘附分子的表达有助于相对自由地通过微血管，而带有伪足的活化白细胞和粘附膜蛋白水平升高则被困在微血管中，附着在内皮上并迁移到组织中。在许多疾病中都可以看到白细胞向活化状态的转化。尽管已经充分认识到了由于感染，组织创伤以及非生理生化或生物物理暴露引起的激活机制，但是许多疾病中的激活机制并未被这些传统机制最终确定，并且仍然未知。我们总结了我们最近的证据，表明小肠中消化酶的主要作用和令人惊讶的作用是白细胞激活和微血管紊乱的根本原因。在正常消化食物的过程中，消化酶通过粘膜上皮屏障在肠腔中分隔。当此屏障的通透性增加时，这些强大的降解酶会泄漏到肠壁和全身循环中。消化酶的泄漏例如发生在生理休克和多器官衰竭中。消化酶进入小肠壁会导致自消化过程中肠组织的降解。消化酶和组织/食物片段不仅会激活白细胞，还会引起许多细胞功能障碍。例如，发生膜受体，血浆蛋白和其他生物分子的蛋白水解破坏。我们得出结论，消化酶从肠道的逸出是细胞功能障碍，发病率甚至死亡率的主要来源，包括流变学研究中发现的异常白细胞活化。