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

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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.

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Abbreviations

AP:

acute pancreatitis

PALI:

pancreatitis-associated lung injury

PECAM-1:

platelet endothelial cell adhesion molecule-1 (CD54)

ICAM-1:

intercellular adhesion molecule-1 (CD31)

CD62L:

L-selectin

CD11b:

integrin αM chain or Mac-1 α chain

CD11b/c:

integrin αm and αx subunits

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Acknowledgments

This work was supported by grants from the Swedish Research Council (grant No. 11236), the Crafoord Foundation, Åke Wiberg Foundation, Magnus Bergvall Foundation, Golje Foundation, and Clas Groschinsky Memorial Foundation.

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Authors and Affiliations

  1. Department of Pharmacology, Medical College of Zhejiang University, Hangzhou, China

    Xia Zhao, Marwan Dib & Xiangdong Wang

  2. Department of Tumor Immunology, Lund University, Lund, Sweden

    Bengt Widegren

  3. Department of Surgery, Lund University Hospital, SE-221 85, Lund, Sweden

    Roland Andersson

Authors
  1. Xia Zhao
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  2. Marwan Dib
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  3. Xiangdong Wang
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  4. Bengt Widegren
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  5. Roland Andersson
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Correspondence to Roland Andersson.

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Zhao, X., Dib, M., Wang, X. et al. Influence of Mast Cells on the Expression of Adhesion Molecules on Circulating and Migrating Leukocytes in Acute Pancreatitis-Associated Lung Injury. Lung 183, 253–264 (2005). https://doi.org/10.1007/s00408-004-2538-8

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  • DOI: https://doi.org/10.1007/s00408-004-2538-8

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