Second-hand cigarette smoke inhibits wound healing of the cornea by stimulating inflammation that delays corneal reepithelialization.
Corneal reepithelialization is a key process in preventing abnormal cornea healing and impaired vision. To gain insight into the mechanisms of cigarette smoke-induced corneal epithelial damage, we injured the cornea of mice and exposed the wounds during the healing process to cigarette smoke in a system that mimics second-hand cigarette smoking by humans. Immunolabeling studies showed that in the mice exposed to smoke, fibronectin, an extracellular matrix molecule critical for epithelial cell migration, is not present in the wounded area and that there is an accumulation of neutrophils in the stroma beneath the wound. Furthermore, inflammatory cytokines, such as interleukin-1alpha, increase after injury in the second-hand-smoke-exposed mice. Localized treatment of the wounds with dexamethasone, an anti-inflammatory agent, resulted in improved healing and infiltration of fewer neutrophils into the wounded area. Depletion of neutrophils with nitrogen mustard or treatment of the wounds with proteinase inhibitors have similar effects to those of dexamethasone. In conclusion, the work presented here shows that second-hand cigarette smoke delays corneal reepithelialization and healing by stimulating both neutrophil attraction to the wound site and degradation of extracellular matrix and adhesion molecules that are important for corneal epithelial cell adhesion and migration.
Ma
Chongze
C
Department of Cell Biology and Neuroscience, University of California Riverside, California 92521, USA.
Martins-Green
Manuela
M
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use; D004195:Disease Models, Animal; D019573:Epithelium, Corneal / Q000187:drug effects / Q000293:injuries / Q000473:pathology*; D005131:Eye Injuries / Q000150:complications / Q000188:drug therapy / Q000473:pathology*; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use; D007634:Keratitis / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009883:Ophthalmic Solutions; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
D005938:Glucocorticoids; D009883:Ophthalmic Solutions; D014028:Tobacco Smoke Pollution; D003907:Dexamethasone