کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2542382 1122699 2007 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A journey with Tony Hugli up the inflammatory cascade towards the auto-digestion hypothesis
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
A journey with Tony Hugli up the inflammatory cascade towards the auto-digestion hypothesis
چکیده انگلیسی

My association with Tony Hugli, long-term editor of Immunopharmacology and International Immunopharmacology, came about by a specific and long-standing problem in inflammation research. What is the trigger mechanism of inflammation in physiological shock? This is an important clinical problem due to the high mortality associated with physiological shock. We joined forces in the search of the answer to this question for more than a decade. Our journey eventually led to development of the hypothesis that shock may be associated with pancreatic enzymes, a set of powerful digestive enzymes that are an integral part of human digestion. The digestive enzymes need to be compartmentalized in the lumen of the intestine where they break down a broad spectrum of biological molecules into their building blocks, suitable for molecular transport across the mucosal epithelium into the circulation. The mucosal epithelial barrier is the key element for compartmentalization of the digestive enzymes. But under conditions when the mucosal barrier is compromised, the fully activated digestive enzymes in the lumen of the intestine are transported into the wall of the intestine, starting an auto-digestion process. In the process several classes of mediators are generated that by themselves have inflammatory activity and upon entry into the central circulation generate the hallmarks of inflammation and eventually cause multi-organ failure. Thus, our journey led to a new hypothesis, which is potentially of fundamental importance for death by multi-organ failure. The auto-digestion hypothesis is in line with the century old observation that the intestine plays a special role on shock — indeed it is the organ for digestion. Auto-digestion may be the prize to pay for life-long nutrition.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Immunopharmacology - Volume 7, Issue 14, 20 December 2007, Pages 1845–1851
نویسندگان
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