L-selectin and intercellular adhesion molecule 1 mediate lymphocyte migration to the inflamed airway/lung during an allergic inflammatory response in an animal model of asthma.
T lymphocytes play a critical role in the development of allergic inflammation in asthma. Early in the allergic response, T lymphocytes migrate from the circulation into the lung to initiate and propagate airway inflammation. The adhesion molecules that mediate lymphocyte entry into inflamed lung have not been defined. This study directly examined the roles of L-selectin and intercellular adhesion molecule 1 (ICAM-1) in lymphocyte migration to the lung during an allergic inflammatory response in an animal model of asthma. Short-term (1 hour) in vivo migration assays and various combinations of adhesion molecule-deficient and wild-type mice were used. Migration of in vivo activated lymphocytes into inflamed lung was significantly greater than entry of resting lymphocytes into noninflamed lung (24.5% +/- 2.7% vs 9.5% +/- 1.3%, P =.001). Migration of activated lymphocytes into inflamed lung was inhibited by 30% in the absence of L-selectin (17.3% +/- 1.3%, P =.04), 47% in the absence of cell surface ICAM-1 (13.0% +/- 2.5%, P =.01), and 47% in the absence of endothelial ICAM-1 (13.0% +/- 2.5%, P =.01). Loss of ICAM-1 on both lymphocytes and lung endothelium inhibited lymphocyte migration by 60% (9.8% +/- 1.8%, P =.002). These findings demonstrate clear roles for both L-selectin and ICAM-1 in lymphocyte migration to the lung during an allergic inflammatory response, with ICAM-1 playing a greater role.
Keramidaris
E
E
Department of Immunology, Royal Children's Hospital, Flemington Rd., Parkville, VIC 3052, Australia.
Merson
T D
TD
Steeber
D A
DA
Tedder
T F
TF
Tang
M L
ML
D000818:Animals; D001249:Asthma / Q000276:immunology*; D002465:Cell Movement; D004195:Disease Models, Animal; D006967:Hypersensitivity / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D019041:L-Selectin / Q000502:physiology*; D008168:Lung / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology*
D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin; D010047:Ovalbumin