Lymphocyte function-associated antigen-1-dependent inhibition of corneal wound healing.
Abrasion of murine corneal epithelium induces neutrophil emigration through limbal vessels into the avascular corneal stroma, peaking within 12 to 18 hours after wounding. A central corneal wound closes within 24 hours by epithelial cell migration and division, and during wound closure corneal epithelial cells express intercellular adhesion molecule (ICAM)-1 (CD54). We investigated the contributions of lymphocyte function-associated antigen (LFA)-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) by analyzing wound closure in mice with targeted deletions of CD11a (CD11a-/-) or CD11b (CD11b-/-). In contrast to CD11a-/- mice, CD11b deficiency revealed a much greater delay in epithelial wound closure with >90% inhibition of epithelial cell division at a time when neutrophil accumulation in the cornea was approximately threefold higher than normal. Treating CD11b-/- mice with anti-CD11a monoclonal antibody at the time of epithelial abrasion resulted in significant reductions in neutrophils and significant increases in corneal epithelial cell division and migration. Treating CD11b-/- mice with anti-ICAM-1 significantly increased measures of healing but marginally reduced neutrophil influx. In conclusion, wound healing after corneal epithelial abrasion is disrupted by the absence of CD11b. The disruption is apparently linked to excessive neutrophil accumulation at a time when epithelial division is essential to wound repair, and neutrophils appear to be detrimental through processes involving LFA-1 and ICAM-1.
Li
Zhijie
Z
Section of Leukocyte Biology, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030-2600, USA.
Burns
Alan R
AR
Smith
C Wayne
CW
D000818:Animals; D040881:CD11a Antigen / Q000276:immunology; D039481:CD11b Antigen / Q000276:immunology; D002455:Cell Division; D002465:Cell Movement; D019573:Epithelium, Corneal / Q000166:cytology / Q000473:pathology* / Q000648:ultrastructure; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D007700:Kinetics; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000276:immunology; D013997:Time Factors; D014945:Wound Healing / Q000502:physiology*
D040881:CD11a Antigen; D039481:CD11b Antigen; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1