Delayed wound healing in the absence of intercellular adhesion molecule-1 or L-selectin expression.
Inflammatory cells play a crucial role in wound healing, but the role of adhesion molecules including L-selectin and intercellular adhesion molecule-1 (ICAM-1) is not known in this process. We examined skin wound repair of excisional wounds in mice lacking L-selectin, ICAM-1, or both. The loss of ICAM-1 inhibited wound healing, keratinocyte migration from the edges of the wound toward the center, and granulation tissue formation. By contrast, L-selectin deficiency alone did not affect any of these parameters. However, the loss of both L-selectin and ICAM-1 resulted in inhibition of keratinocyte migration and granulation tissue formation beyond those caused by loss of ICAM-1 alone. Treatment of platelet-derived growth factor to the wounds normalized delayed wound healing in ICAM-1(-/-) mice, but not in L-selectin/ICAM-1(-/-) mice. Therefore, although ICAM-1 contributes to wound repair to a greater extent than L-selectin, a role for L-selectin was revealed in the absence of ICAM-1. The impaired wound repair was associated with reduced infiltration of neutrophils and macrophages in ICAM-1(-/-) and L-selectin/ICAM-1(-/-) mice. These results demonstrate a distinct role of ICAM-1 and L-selectin in wound healing and that the delayed wound healing in the absence of these molecules is likely because of decreased leukocyte accumulation into the wound site.
Nagaoka
T
T
Department of Dermatology, Kanazawa University School of Medicine, Ishikawa, Japan.
Kaburagi
Y
Y
Hamaguchi
Y
Y
Hasegawa
M
M
Takehara
K
K
Steeber
D A
DA
Tedder
T F
TF
Sato
S
S
D000818:Animals; D002452:Cell Count; D002465:Cell Movement; D005260:Female; D015870:Gene Expression; D006097:Granulation Tissue; D006133:Growth Substances / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D019041:L-Selectin / Q000235:genetics*; D008264:Macrophages / Q000166:cytology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000166:cytology; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics*
D006133:Growth Substances; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin