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Published online before print September 4, 2007

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(Journal of Leukocyte Biology. 2007;82:1554-1563.)
© 2007 by Society for Leukocyte Biology

Accelerated wound healing in leukocyte-specific, protein 1-deficient mouse is associated with increased infiltration of leukocytes and fibrocytes

JianFei Wang^*, Haiyan Jiao^*, Tara L. Stewart^*, Megan V. H. Lyons^*, Heather A. Shankowsky^*, Paul G. Scott and Edward E. Tredget^*,1

^* Wound Healing Research Group Division of Plastic and Reconstructive Surgery and Critical Care, Department of Surgery, and
Department of Biochemistry, University of Alberta, Edmonton, Canada

¹Correspondence: 2D3.81 WMSHC, 8440-112 St., University of Alberta, Edmonton, Alberta T6G 2B7, Canada. E-mail: etredget{at}ualberta.ca

Wound healing is a complex process involving the integrated actions of numerous cell types, soluble mediators, and ECM. Recently, a newly identified cell type, the fibrocyte, has been reported to contribute to wound healing and fibrotic conditions such as hypertrophic scarring. We previously established leukocyte-specific protein 1 (LSP1) as a marker for fibrocytes. LSP1 is an F-actin binding protein and substrate of p38 mitogen-activated protein kinase and protein kinase C, and has been reported to be important in leukocyte chemotaxis. We examine the biological roles of LSP1 in skin wound healing using Lsp1^–/– null mice. These animals showed accelerated healing of full-thickness skin wounds, with increased re-epithelialization rates, collagen synthesis, and angiogenesis. Healing wounds in Lsp1^–/– mice had higher densities of neutrophiles, macrophages, and fibrocytes. Along with increased leukocyte infiltration, levels of macrophage-derived chemokine expression, TGF-β1, and VEGF were all up-regulated. These results demonstrate that the absence of LSP1 promotes healing of skin wounds. The primary mechanism seems to be an increase in leukocyte infiltration, leading to locally elevated synthesis and release of chemokines and growth factors. Further analysis of Lsp1^–/– mice may suggest ways to improve wound healing and/or treat fibrotic conditions of skin and other tissue.

Key Words: extracellular matrix molecule • LSP1 • fibrotic disease • cytoskeletal protein