Journal of Applied Physiology Journal of Applied Physiology
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J Appl Physiol 83: 681-687, 1997;
8750-7587/97 $5.00
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Journal of Applied Physiology
Vol. 83, No. 3, pp. 681-687, September 1997
CELLULAR ASPECTS OF LUNG FUNCTION

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

George T. De Sanctis1, Walter W. Wolyniec2, Francis H. Y. Green3, Shixin Qin4, Aiping Jiao1, Patricia W. Finn1, Thomas Noonan2, Anthony A. Joetham6, Erwin Gelfand6, Claire M. Doerschuk5, and Jeffrey M. Drazen1,5

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 Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; and 6 Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206

Received 20 December 1996; accepted in final form 22 April 1997.

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.

asthma; bronchoconstriction; methacholine; ovalbumin; knockout

0161-7567/97 $5.00 Copyright © 1997 the American Physiological Society




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