Resolution of lung inflammation by CD44.
Successful repair after tissue injury and inflammation requires resolution of the inflammatory response and removal of extracellular matrix breakdown products. We have examined whether the cell-surface adhesion molecule and hyaluronan receptor CD44 plays a role in resolving lung inflammation. CD44-deficient mice succumb to unremitting inflammation following noninfectious lung injury, characterized by impaired clearance of apoptotic neutrophils, persistent accumulation of hyaluronan fragments at the site of tissue injury, and impaired activation of transforming growth factor-beta1. This phenotype was partially reversed by reconstitution with CD44+ cells, thus demonstrating a critical role for this receptor in resolving lung inflammation.
Teder
Priit
P
Department of Medicine, Pulmonary and Critical Care Section, Yale University School of Medicine, New Haven, CT 06520, USA.
Vandivier
R William
RW
Jiang
Dianhua
D
Liang
Jiurong
J
Cohn
Lauren
L
Puré
Ellen
E
Henson
Peter M
PM
Noble
Paul W
PW
D000818:Animals; D017209:Apoptosis; D001761:Bleomycin; D016026:Bone Marrow Transplantation; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D002678:Chimera; D006801:Humans; D018960:Hyaluronan Receptors / Q000502:physiology*; D006820:Hyaluronic Acid / Q000032:analysis / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D017563:Lung Diseases, Interstitial / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D009504:Neutrophils; D010587:Phagocytosis; D010641:Phenotype; D011650:Pulmonary Alveoli / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
D018925:Chemokines; D018960:Hyaluronan Receptors; D012333:RNA, Messenger; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; D006820:Hyaluronic Acid