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Endothelial selectins regulate skin wound healing in cooperation with L‐selectin and ICAM‐1
Author(s) -
Yukami Toru,
Hasegawa Minoru,
Matsushita Yukiyo,
Fujita Tomoyuki,
Matsushita Takashi,
Horikawa Mayuka,
Komura Kazuhiro,
Yanaba Koichi,
Hamaguchi Yasuhito,
Nagaoka Tetsuya,
Ogawa Fumihide,
Fujimoto Manabu,
Steeber Douglas A.,
Tedder Thomas F.,
Takehara Kazuhiko,
Sato Shinichi
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0307152
Subject(s) - selectin , wound healing , cell adhesion molecule , angiogenesis , icam 1 , granulation tissue , intercellular adhesion molecule 1 , immunology , biology , basic fibroblast growth factor , p selectin , cytokine , cell adhesion , inflammation , cancer research , microbiology and biotechnology , growth factor , cell , receptor , biochemistry , platelet , platelet activation
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‐β 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.