Gelatinase B is involved in the in vitro wound repair of human respiratory epithelium.
Following epithelial injury, extracellular matrix undergoes imposing remodelings. We examined the contribution of matrix metalloproteinases, gelatinases A and B, in an in vitro wound repair model of human respiratory epithelium. Confluent human surface respiratory epithelial (HSRE) cells cultured from dissociated surface cells of human nasal polyps were chemically injured. Over the next 3 to 5 days, cells migrated onto the injured area to repair the circular wound. Repair kinetics of these wounds was monitored until wound closure occurred. Gelatinolytic activities were analysed in culture supernates and in cell protein extracts derived from repairing migratory and non repairing stationary cells. Small amounts of gelatinase A were expressed by HSRE cells, and variations of this gelatinase remained very weak for the time of the wound repair. In contrast, gelatinase B was upregulated during the wound repair process, with a maximum peak observed at wound closure. A marked gelatinase B activation occurred only in cells involved in the repair process. Gelatinase B was localized in some migratory basal cells, recognized by an anti-cytokeratin 14 antibody and located around the wound. We could not detect any gelatinase A in repairing or in stationary HSRE cells. Addition of the 6-6B monoclonal antibody, known to inhibit gelatinase B activation, to the culture medium during the repair process resulted in a dose-dependent decrease of the wound repair speed. These results suggest that gelatinase B, produced by epithelial cells, actively contributes to the wound repair process of the respiratory epithelium.
Buisson
A C
AC
Unité INSERM 314, Université de Reims, France.
Zahm
J M
JM
Polette
M
M
Pierrot
D
D
Bellon
G
G
Puchelle
E
E
Birembaut
P
P
Tournier
J M
JM
D000328:Adult; D002478:Cells, Cultured; D017364:Collagenases / Q000378:metabolism*; D004789:Enzyme Activation; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000378:metabolism; D009297:Nasal Mucosa / Q000166:cytology / Q000502:physiology*; D014018:Tissue Distribution; D014945:Wound Healing
D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9