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Enterohepatic recirculation of bile is pivotal for homoeostatic functions in the gastrointestinal tract (Zeuzem, 2000). Cholestasis triggers immediate liver injury and the absence of bile in the intestine facilitates bacterial translocation, which, in turn, may cause sepsis and further liver injury (Ding et al., 1994; Chand and Sanyal, 2007). In this vicious cycle, leukocyte recruitment has emerged as a key feature in the pathogenesis of cholestatic liver injury (Gujral et al., 2003, 2004; Laschke et al.

, 2007) although the adhesive mechanisms behind leukocyte accumulation in obstructive jaundice remain elusive. Leukocytes extravasate from the hepatic microcirculation, which consists of a mixed hepatic arterial and portal venous inflow system, a low-pressure sinusoidal perfusion and blood drainage by postsinusoidal venules. In general, early steps in the leukocyte extravasation process are mediated by the selectin family of adhesion molecules (L-, E- and P-selectin) and their respective glycoprotein counterligands (Vestweber and Blanks, 1999). Some investigators, however, have suggested that early leukocyte�Cendothelium interactions, at least in hepatic sinusoids, may be selectin independent (Wong et al., 1997) due to the lack of P-selectin on sinusoidal endothelial cells (Steinhoff et al., 1993; Essani et al.

, 1998; Massaguer et al., 2002). Nonetheless, P-selectin function appears to be critical in reperfusion- and endotoxin-mediated leukocyte recruitment, liver damage and intrahepatic cholestasis (Sawaya et al., 1999; Klintman et al., 2004; Laschke et al., 2007). In contrast, the role of P-selectin in cholestasis-induced leukocyte accumulation, sinusoidal perfusion failure and hepatic tissue injury is not known. Platelets have been considered to be essential for haemostasis although accumulating data also suggest a role in inflammation and tissue injury (von Hundelshausen and Weber, 2007). Of interest, some recent studies have reported that platelets may exert a role in microvascular leukocyte recruitment (Salter et al., 2001; Singbartl et al., 2001).

Accordingly, depletion of platelets has been shown to decrease pulmonary leukocyte accumulation in models of allergic inflammation and hydrochloric acid-induced lung damage (Pitchford et al., 2004, 2005; Zarbock et al., 2006). The detailed mechanisms of this platelet-mediated accumulation of leukocytes in the lung are still under investigation but may be related to the formation of platelet�Cleukocyte aggregates within the systemic circulation. Adhesion Dacomitinib between platelets and leukocytes results in reciprocal cell activation (Abou-Saleh et al.