A role for CD44 in an antigen-induced murine model of pulmonary eosinophilia.
Previous studies established that IL-5-producing CD4(+) T cells play a pivotal role in allergic respiratory inflammation. It was also reported that CD4(+) T cells express higher levels of CD44 in the airway than in peripheral blood of patients with allergic respiratory diseases. We have used experimental pulmonary eosinophilia induced in mice by Ascaris suum (Asc) extract to investigate the role of CD44 in the development of allergic respiratory inflammation. Intraperitoneal administration of anti-CD44 mAb prevented both lymphocyte and eosinophil accumulation in the lung. Anti-CD44 mAb also blocked antigen-induced elevation of Th2 cytokines as well as chemokines (CCL11, CCL17) in bronchoalveolar lavage fluid (BALF). Treatment with anti-CD44 mAb inhibited the increased levels of hyaluronic acid (HA) and leukotriene concentrations in BALF that typically result from antigen challenge. Anti-CD44 mAb also blocked antigen-induced airway hyperresponsiveness. An anti-CD44 mAb (IM7) inhibited the HA-binding ability of splenocytes associated with decreased levels of CD44. Soluble CD44 levels in serum were increased in Asc-challenged IM7-treated mice, but not in KM201-treated mice, compared with Asc-challenged rat IgG-treated mice. Ab's that block CD44-HA binding reduced allergic respiratory inflammation by preventing lymphocyte and eosinophil accumulation in the lung. Thus, CD44 may be critical for development of allergic respiratory inflammation.
Third Department of Internal Medicine, Miyazaki Medical College, Miyazaki, Japan. kshigeki@post1.miyazaki-med.ac.jp
Shigeki
S
Katoh
Nobuhiro
N
Matsumoto
Kumiko
K
Kawakita
Akira
A
Tominaga
Paul W
PW
Kincade
Shigeru
S
Matsukura
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D039741:Antigens, Dermatophagoides; D000947:Antigens, Helminth; D001853:Bone Marrow / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D016084:Bronchoconstriction / Q000187:drug effects; D016085:Bronchoconstrictor Agents; D002452:Cell Count; D018925:Chemokines / Q000032:analysis; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects; D018960:Hyaluronan Receptors / Q000032:analysis / Q000276:immunology* / Q000502:physiology*; D006820:Hyaluronic Acid / Q000032:analysis; D015289:Leukotrienes / Q000032:analysis; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D011657:Pulmonary Eosinophilia / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control
D000911:Antibodies, Monoclonal; D039741:Antigens, Dermatophagoides; D000947:Antigens, Helminth; D016085:Bronchoconstrictor Agents; D018925:Chemokines; D016207:Cytokines; D018960:Hyaluronan Receptors; D015289:Leukotrienes; D006820:Hyaluronic Acid