Role of very late adhesion integrins in mediating repair of human airway epithelial cell monolayers after mechanical injury.
Repair of the airway epithelium after injury requires that processes such as adhesion and cell migration occur in a defined order. Both of these processes depend on interactions between extracellular matrix (ECM) proteins and appropriate integrins. To study these interactions, we examined monolayer wound repair in a cultured human airway epithelial cell line, 16HBE14o-. Wounds created in confluent monolayers grown on either collagen-IV, laminin-1, or laminin-2 matrix closed quickly in response to 15 ng/ml epidermal growth factor (EGF). Concurrent treatment of cells grown on each matrix protein with EGF and a monoclonal antibody (mAb) to beta1-integrin inhibited wound closure. Treatment with a mAb to alpha2-, alpha3-, and alpha6-integrin blocked wound repair in monolayers grown on collagen-IV but did not do so in monolayers grown either on laminin-1 or laminin-2. Inhibition was not due to cell detachment or apoptosis. These data demonstrate that integrins expressed by airway epithelial cells mediate wound closure on different constitutive ECM proteins. These data suggest that beta1-integrin subunit function is required to permit migration and spreading of epithelial cells, and that alpha-integrin subunits alone do not mediate migration of epithelial cells grown on either laminin-1 or laminin-2. These differences may become important if the matrix protein composition of airway basement membrane changes in disease states such as asthma.
White
S R
SR
Section of Pulmonary and Critical Care Medicine, Department of Medicine, Division of Biological Sciences, University of Chicago, Chicago, Illinois, USA. swhite@medicine.bsd.uchicago.edu
Dorscheid
D R
DR
Rabe
K F
KF
Wojcik
K R
KR
Hamann
K J
KJ
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis; D001980:Bronchi; D002455:Cell Division; D002461:Cell Line, Transformed; D003094:Collagen / Q000502:physiology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D019012:Integrin beta1 / Q000276:immunology / Q000502:physiology*; D007797:Laminin / Q000502:physiology; D016029:Receptors, Very Late Antigen / Q000096:biosynthesis / Q000502:physiology*; D013539:Simian virus 40; D014945:Wound Healing
D000911:Antibodies, Monoclonal; D016326:Extracellular Matrix Proteins; D019012:Integrin beta1; D007797:Laminin; D016029:Receptors, Very Late Antigen; D004815:Epidermal Growth Factor; D003094:Collagen