Reduction of allergic airway responses in P-selectin-deficient mice.
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.
De Sanctis
G T
GT
Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Wolyniec
W W
WW
Green
F H
FH
Qin
S
S
Jiao
A
A
Finn
P W
PW
Noonan
T
T
Joetham
A A
AA
Gelfand
E
E
Doerschuk
C M
CM
Drazen
J M
JM
D000403:Airway Resistance / Q000502:physiology; D000818:Animals; D000917:Antibody Formation / Q000235:genetics / Q000502:physiology; D016535:Bronchial Hyperreactivity / Q000473:pathology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D007073:Immunoglobulin E / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D019007:P-Selectin / Q000235:genetics* / Q000378:metabolism*; D012130:Respiratory Hypersensitivity / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D012137:Respiratory System / Q000378:metabolism / Q000473:pathology
D016207:Cytokines; D019007:P-Selectin; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin