Reduction of allergic airway responses in P-selectin-deficient mice

Author:

De Sanctis George T.1,Wolyniec Walter W.2,Green Francis H. Y.3,Qin Shixin4,Jiao Aiping1,Finn Patricia W.1,Noonan Thomas2,Joetham Anthony A.5,Gelfand Erwin5,Doerschuk Claire M.6,Drazen Jeffrey M.16

Affiliation:

1. Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115;

2. Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877;

3. Respiratory Research Group, University of Calgary, Calgary, Alberta, Canada T2N 4N1;

4. Leukosite, Inc., Cambridge, Massachusetts 02142;

5. Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206

6. Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; and

Abstract

De Sanctis, George T., Walter W. Wolyniec, Francis H. Y. Green, Shixin Qin, Aiping Jiao, Patricia W. Finn, Thomas Noonan, Anthony A. Joetham, Erwin Gelfand, Claire M. Doerschuk, and Jeffrey M. Drazen. Reduction of allergic airway responses in P-selectin-deficient mice. J. Appl. Physiol. 83(3): 681–687, 1997.—P-selectin is an adhesion receptor that has been shown to be important in the recruitment of eosinophils and lymphocytes in a variety of inflammatory conditions. Because cellular recruitment is thought to be a critical event in allergen-induced changes in airway responsiveness, we reasoned that P-selectin-deficient mice would exhibit reduced airway responsiveness and cellular trafficking noted in wild-type (+/+) mice. Both (+/+) and P-selectin-deficient (−/−) mice sensitized and challenged with ovalbumin (OVA/OVA) exhibited the same capacity to produce increased titers of total and OVA-specific immunoglobulin E. Airway responsiveness to methacholine was significantly greater in the (+/+) (OVA/OVA) animals than it was in the respective (−/−) (OVA/OVA) group or control groups ( P = 0.0016). Bronchoalveolar lavage fluid from (−/−) (OVA/OVA) mice contained significantly fewer eosinophils and lymphocytes compared with the (+/+) (OVA/OVA) mice ( P < 0.05). These results suggest that the predominant role of P-selectin in OVA-induced airway hyperresponsiveness is to promote the airway inflammatory response to allergen inhalation.

Publisher

American Physiological Society

Subject

Physiology (medical),Physiology

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