E- and P-selectins are essential for the development of cockroach allergen-induced airway responses.
Peribronchial inflammation contributes to the pathophysiology of allergic asthma. In many vascular beds, adhesive interactions between leukocytes and the endothelial surface initiate the recruitment of circulating cells. Previous studies using OVA-induced airway hyperreactivity indicated that P-selectin, a member of the selectin family expressed by activated platelets and endothelium, contributed to both inflammation and bronchoconstriction. The current study used cockroach allergen (CRA), an allergen that induces asthmatic responses in both humans and mice, to further investigate the role of selectins in the development of peribronchial inflammation and airway hyperreactivity. P- and E-selectin mRNAs were detected in extracts of CRA-sensitized animals beginning shortly after intratracheal challenge with CRA. The P-selectin mRNA was transiently induced at early time points while up-regulation of the E-selectin mRNA was more prolonged. Mice with targeted deletions in E-selectin (E(-)), P-selectin (P(-)), and both genes (E(-)/P(-)) showed 70-85% reductions in airway hyperreactivity, peribronchial inflammation, and eosinophil accumulation. The P(-) and E(-)/P(-) groups showed the most profound reductions. The transfer of splenic lymphocytes from CRA-primed E(-)/P(-) into naive wild-type (WT) mice produced the same level of airway hyperreactivity as transfers from CRA-primed WT into naive WT hosts, indicating that peripheral immunization was similar. The observed changes in the selectin-deficient animals were not related to inadequate sensitization, because CRA priming and challenge increased serum IgE levels. Furthermore, pulmonary Th2-type cytokines and chemokines in the E-selectin(-/-) and WT animals were similar. The findings indicate that both P- and E-selectin contribute to CRA-induced peribronchial inflammation and airway hyperreactivity.
Lukacs
Nicholas W
NW
Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA. nlukacs@umich.edu
John
Alison
A
Berlin
Aaron
A
Bullard
Daniel C
DC
Knibbs
Randall
R
Stoolman
Lloyd M
LM
D019264:Adoptive Transfer; D000485:Allergens / Q000008:administration & dosage*; D000818:Animals; D052179:Antigens, Plant; D001249:Asthma / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000276:immunology; D003058:Cockroaches / Q000276:immunology; D019040:E-Selectin / Q000235:genetics / Q000276:immunology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019007:P-Selectin / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D000485:Allergens; D052179:Antigens, Plant; D019040:E-Selectin; D019007:P-Selectin; D012333:RNA, Messenger; C060835:allergen CRa, cockroach