Influence of Mast Cells on the Expression of Adhesion Molecules on Circulating and Migrating Leukocytes in Acute Pancreatitis-Associated Lung Injury

Abstract

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.

Time course of skin features and inflammatory biomarkers after liquid sulfur mustard exposure in SKH-1 hairless mice

“…Mast cells being important sources of cytokines and chemokines, previous studies have shown in several models of inflammation that these cells play a central role in neutrophils recruitment at sites of injury by delivering TNFa and MIP-2 (Biedermann et al, 2000;Malaviya et al, 1996) or KC (Schramm et al, 2002). Likewise, mast cells may also influence the expression of adhesion molecules and thus the recruitment of neutrophil (Zhao et al, 2005). So, our results suggest that mast cells activation is an early event related to the dose of exposure in SM-induced skin injury, defining the intensity of inflammatory response and modulating the neutrophil influx through secretion of specific cytokines.…”

Mast-Cell-Releasing Tryptase Triggers Acute Lung Injury Induced by Small Intestinal Ischemia–Reperfusion by Activating PAR-2 in Rats

“…It is well known that neutrophil sequestration is implicated in IIR-mediated ALI [34], meanwhile, it has also been reported that treatment with mast cell stabilizer cromolyn sodium can dramatically decrease expressions of ICAM-1 on pulmonary neutrophils in pancreatitisassociated lung injury [20]. Unfortunately, the limitation of the present study did not show the relationships between the mast cell degranulation and neutrophil migration in the development of IIR-mediated ALI.…”

“…Moreover, Zhao et al have discovered that mast cells are involved in acute pancreatitis-associated lung injury and pretreatment with mast cell stabilizing agents has showed protective effects [20]. Unfortunately, those studies did not specialize the precise function of tryptase during ischemia-reperfusion injury, thus, we speculated that tryptase released from mast cell degranulation would be implicated in acute lung injury during small intestinal ischemia-reperfusion injury.…”

A new understanding of pancreatitis-associated pulmonary injury

“…Expression of CD11b or CD11b/c on leukocytes from blood, lung tissue and bronchoalveolar lavage fluid (BALF) increased after induction of AP (20). It seems that expression of CD11b or CD11b/c on circulating leukocytes correlates with leukocyte infiltration in lung tissue as well as plasma exudation.…”

“…Moderate alterations in the expression of L-selectin were noted on both neutrophils and monocytes/macrophages from the circulation and lung tissue. Administration of the mast cell stabilizer downregulated the expression of these adhesion molecules on both neutrophils and monocytes/macrophages (20), indicating that activation of local mast cells plays an important role in leukocyte orientation and activation in the lungs.…”