Integrin alpha(3)-subunit expression modulates alveolar epithelial cell monolayer formation.
We investigated expression of the alpha(3)-integrin subunit by rat alveolar epithelial cells (AECs) grown in primary culture as well as the effects of monoclonal antibodies with blocking activity against the alpha(3)-integrin subunit on AEC monolayer formation. alpha(3)-Integrin subunit mRNA and protein were detectable in AECs on day 1 and increased with time in culture. alpha(3)- and beta(1)-integrin subunits coprecipitated in immunoprecipitation experiments with alpha(3)- and beta(1)-subunit-specific antibodies, consistent with their association as the alpha(3)beta(1)-integrin receptor at the cell membrane. Treatment with blocking anti-alpha(3) monoclonal antibody from day 0 delayed development of transepithelial resistance, reduced transepithelial resistance through day 5 compared with that in untreated AECs, and resulted in large subconfluent patches in monolayers viewed by scanning electron microscopy on day 3. These data indicate that alpha(3)- and beta(1)-integrin subunits are expressed in AEC monolayers where they form the heterodimeric alpha(3)beta(1)-integrin receptor at the cell membrane. Blockade of the alpha(3)-integrin subunit inhibits formation of confluent AEC monolayers. We conclude that the alpha(3)-integrin subunit modulates formation of AEC monolayers by virtue of the key role of the alpha(3)beta(1)-integrin receptor in AEC adhesion.
Lubman
R L
RL
Division of Pulmonary and Critical Care Medicine and Will Rogers Institute Pulmonary Research Center, University of Southern California, Los Angeles, California 90033, USA. rlubman@hsc.usc.edu
Zhang
X L
XL
Zheng
J
J
Ocampo
L
L
Lopez
M Z
MZ
Veeraraghavan
S
S
Zabski
S M
SM
Danto
S I
SI
Borok
Z
Z
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D015152:Blotting, Northern; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002467:Cell Nucleus / Q000648:ultrastructure; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000502:physiology / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D039422:Integrin alpha3; D016023:Integrins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008855:Microscopy, Electron, Scanning; D011233:Precipitin Tests; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000502:physiology / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D039422:Integrin alpha3; D016023:Integrins