PT  - JOURNAL ARTICLE
AU  - E Ryschich
AU  - V Kerkadze
AU  - O Deduchovas
AU  - O Salnikova
AU  - A Parseliunas
AU  - A Märten
AU  - W Hartwig
AU  - M Sperandio
AU  - J Schmidt
TI  - Intracapillary leucocyte accumulation as a novel antihaemorrhagic mechanism in acute pancreatitis in mice
AID  - 10.1136/gut.2008.170001
DP  - 2009 Nov 01
TA  - Gut
PG  - 1508--1516
VI  - 58
IP  - 11
4099  - http://gut.bmj.com/content/58/11/1508.short
4100  - http://gut.bmj.com/content/58/11/1508.full
SO  - Gut2009 Nov 01; 58
AB  - Background: Pancreatic infiltration by leucocytes represents a hallmark in acute pancreatitis. Although leucocytes play an active role in the pathophysiology of this disease, the relation between leucocyte activation, microvascular injury and haemorrhage has not been adequately addressed.Methods: We investigated intrapancreatic leucocyte migration, leucocyte extravasation and pancreatic microperfusion in different models of oedematous and necrotising acute pancreatitis in lys-EGFP-ki mice using fluorescent imaging and time-lapse intravital microscopy.Results: In contrast to the current paradigm of leucocyte recruitment, the initial event of leucocyte activation in acute pancreatitis was represented through a dose- and time-dependent occlusion of pancreatic capillaries by intraluminally migrating leucocytes. Intracapillary leucocyte accumulation (ILA) resulted in dense filling of almost all capillaries close to the area of inflammation and preceded transvenular leucocyte extravasation. ILA was also initiated by isolated exposure of the pancreas to interleukin 8 or fMLP, demonstrating the causal role of chemotactic stimuli in the induction of ILA. The onset of intracapillary leucocyte accumulation was strongly inhibited in LFA-1−/− and ICAM-1−/− mice, but not in Mac-1−/− mice. Moreover, prevention of intracapillary leucocyte accumulation led to the development of massive capillary haemorrhages and transformed mild pancreatitis into lethal haemorrhagic disease.Conclusions: ILA represents a novel protective and potentially lifesaving mechanism of haemostasis in acute pancreatitis. This process depends on expression of LFA-1 and ICAM-1 and precedes the classical steps of the leucocyte recruitment cascade.