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Endothelial selectins regulate skin wound healing in cooperation with L-selectin and ICAM-1.
- Source :
-
Journal of leukocyte biology [J Leukoc Biol] 2007 Sep; Vol. 82 (3), pp. 519-31. Date of Electronic Publication: 2007 Jun 26. - Publication Year :
- 2007
-
Abstract
- Skin wound healing is mediated by inflammatory cell infiltration that is highly regulated by various adhesion molecules. Mice lacking intercellular adhesion molecule-1 (ICAM-1) delayed skin wound healing and mice lacking both L-selectin and ICAM-1 (L-selectin/ICAM-1(-/-)) show more delayed wound healing. Deficiency of both endothelial selectins (E-selectin or P-selectin) also delays wound healing. However, the relative contribution and interaction of selectins and ICAM-1 to the wound healing remain unknown. To clarify them, repair of excisional wounds was examined in L-selectin/ICAM-1(-/-) mice, wild-type mice with both E- and P-selectin blockade, and L-selectin/ICAM-1(-/-) mice with both E- and P-selectin blockade. Wild-type mice with both E- and P-selectin blockade showed delayed wound healing that was comparable with that in L-selectin/ICAM-1(-/-) mice. Combined E- and P-selectin blockade in L-selectin/ICAM-1(-/-) mice resulted in more significant delay. Mice lacking or blocked for adhesion molecules also showed suppressed keratinocyte migration, angiogenesis, granulation tissue formation, leukocyte infiltration, and cytokine expression, including transforming growth factor-beta and interleukin-6. Application of basic fibroblast growth factor (bFGF) but not platelet-derived growth factor to the wounds significantly improved wound healing in L-selectin/ICAM-1(-/-) mice with both E- and P-selectin blockade. bFGF significantly increased the leukocyte infiltration and subsequent fibrogenic cytokine production, as well as keratinocyte migration, angiogenesis, and collagen synthesis despite the loss of four kinds of adhesion molecules. These results indicate that skin wound healing is regulated cooperatively by all selectins and ICAM-1 and may provide critical information for the therapy of skin wounds.
- Subjects :
- Animals
Cell Movement
Collagen genetics
Collagen metabolism
Cytokines metabolism
E-Selectin genetics
Female
Fibroblast Growth Factor 2
Granulation Tissue pathology
Intercellular Adhesion Molecule-1 genetics
L-Selectin genetics
Macrophages cytology
Macrophages metabolism
Male
Mast Cells cytology
Mast Cells metabolism
Mice
Mice, Knockout
Neovascularization, Physiologic
Neutrophil Infiltration
P-Selectin genetics
P-Selectin metabolism
RNA, Messenger genetics
RNA, Messenger metabolism
Skin cytology
E-Selectin metabolism
Intercellular Adhesion Molecule-1 physiology
L-Selectin physiology
Skin metabolism
Wound Healing physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0741-5400
- Volume :
- 82
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of leukocyte biology
- Publication Type :
- Academic Journal
- Accession number :
- 17595378
- Full Text :
- https://doi.org/10.1189/jlb.0307152