Pancreatitis-associated
lung injury is an early-occurring and severe complication, still associated with substantial mortality. A number of inflammatory cells and their products are involved in the initiation and progress of the condition. In the present study,
acute pancreatitis (AP) was induced by the intraductal infusion of 5%
sodium taurodeoxycholate in the rat. Pulmonary endothelial barrier dysfunction was measured by plasma exudation of radiolabeled
albumin. Expression of
PECAM-1,
ICAM-1, and
L: -selectin on neutrophils (CD11b(+)) and monocytes/macrophages (CD11b/c(+)), obtained from circulation and lung tissue, was measured 1 and 6 hours after AP induction (n = 10 rats/time point/group). Plasma levels of
histamine and
serotonin were determined. The role of mast cells was evaluated by pretreatment with the
mast cell stabilizer cromolyn. Intraperitoneal administration of
cromolyn downregulated
pancreatitis-induced systemic increase of
histamine at 1 hour (513 +/- 82 vs. 309 +/- 50, p < 0.05).
Cromolyn prevented a decreased expression of
PECAM-1 on circulatory neutrophils and monocytes/macrophages and against an increased expression of
ICAM-1 and
PECAM-1 on pulmonary neutrophils and monocytes/macrophages 6 hours after AP induction (about 40% vs. 10%, p < 0.01). The
mast cell stabilizer also prevented
pancreatitis-induced pulmonary endothelial barrier dysfunction at 6 hours. Thus, our data indicate that mast cells may play a critical role in the activation of leukocytes during the initiation of
pancreatitis-associated
lung injury by altering phenotypes of adhesion molecules.