Mast cell: pivotal player in lethal acute pancreatitis.

Abstract

The fearful aura of acute pancreatitis stems from the imagery of an organ and organism under threat of cannibalization by pancreatic enzymes that have become active prematurely. This century‐old autodigestion theory1 is all too plausible when one is confronted with the necrohaemorrhagic remains of the gland in a patient who succumbs from multisystem organ failure, as do 10–20% of cases. It was challenged2 when the average interval from onset of symptoms to death was found to be shorter (under 48 h) and the degree of initial shock greater with interstitial pancreatitis—which accounts for a quarter of the toll3—than with wholesale coagulative necrosis, an infarct‐like lesion associated with hyaline occlusion of venules and capillaries.2 The literature is colossal—4844 titles in a Medline search from 1966, and 260 in 1999—but the current position can be gleaned from a recent monograph,4 an assortment of reviews5–,11 and supplementary papers. Of necessity, much reliance has been placed on studies of experimental pancreatitis to unravel the earliest aberrations. From these and clinical studies, it is now believed that the ‘attack’ begins in the acinar cell, with a functional blockade in the secretory pathway towards exocytosis of zymogen granules. It is also agreed that multiorgan collapse is primarily due to hyperinflammation, abetted by activation of coagulation, fibrinolytic, kallikrein‐kinin and complement enzyme cascades with consumption of α2 macroglobulin (α2M). The debate concerns the nature of the trigger mechanism and why it should evoke an exaggerated inflammatory reaction and cause (subclinical) disturbances in distant organs even when the disease seems to be mild. In the latter context, the injured acinar cell is now known to step up its production of platelet‐activating factor (PAF)—a physiological secretagogue but which at high doses inhibits secretion—and to synthesize heat‐shock and acute‐phase proteins, …