Decreased macrophage number and activation lead to reduced lymphatic vessel formation and contribute to impaired diabetic wound healing

Kazuichi Maruyama, Jun Asai, Masaaki Ii, Tina Thorne, Douglas W. Losordo, Patricia A. D'Amore

研究成果: Article査読

354 被引用数 (Scopus)

抄録

Impaired wound healing is a common complication of diabetes. Although it is well known that both macrophages and blood vessels are critical to wound repair, the role of wound-associated lymphatic vessels has not been well investigated. We report that both the presence of activated macrophages and the formation of lymphatic vessels are rate-limiting to the healing of diabetic wounds. We have previously shown that macrophages contribute to the lymphatic vessels that form during the acute phase of corneal wound healing. We now demonstrate that this is a general phenomenon; cells that co-stain for the macrophage marker F4/80 and the lymphatic markers LYVE-1 (lymphatic vascular endothelium hyaluronate receptor) and podoplanin contribute to lymphatic vessels in full-thickness wounds. LYVE-1-positive lymphatic vessels and CD31-positive blood vessels were significantly reduced in corneal wound healing in diabetic mice (db/db) (P < 0.02) compared with control (db/+) mice. Glucose treatment of control macrophages led to the down-regulation of the lymphatic-specific receptor VEGFR3 and its ligands, vascular endothelial growth factor-C and -D (VEGF-C, -D). Interleukin-1β stimulation rescued diabetic macrophage function; application of interleukin-1β-treated db/db-derived macrophages to wounds in db/db mice induced lymphatic vessel formation and accelerated wound healing. These observations suggest a potential therapeutic approach for healing wounds in diabetic patients.

本文言語English
ページ(範囲)1178-1191
ページ数14
ジャーナルAmerican Journal of Pathology
170
4
DOI
出版ステータスPublished - 2007 4月
外部発表はい

ASJC Scopus subject areas

  • 病理学および法医学

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