Journal
JOURNAL OF COMPARATIVE PATHOLOGY
Volume 145, Issue 4, Pages 378-389Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.jcpa.2011.01.012
Keywords
galectin-3; macrophage; myofibroblasts; rat; wound healing
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Funding
- Japanese Society for the Promotion of Science (JSPS) [18380188, 1081000014]
- Grants-in-Aid for Scientific Research [22380173] Funding Source: KAKEN
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The aim of this study was to investigate the properties of macrophages that infiltrated the sites of cutaneous wound healing in rats between 1 and 26 days post wounding (dpw). During the inflammation phase (1-3 dpw), ED1(+) (CD68(+)) macrophages with enhanced lysosomal activity dominated. From 5 to 7 dpw there was formation of granulation tissue as indicated by the presence of myofibroblasts expressing alpha-smooth muscle actin. At this stage, ED2(+) (CD163(+)) macrophages, capable of producing inflammatory factors, were dominant. The majority of ED1(+) macrophages expressed galectin-3, a regulator of fibrosis. Corresponding to the increased numbers of ED1(+) and ED2+ macrophages at 3-9 dpw, there was increased expression of genes encoding transforming growth factor-beta 1 (a major fibrogenic factor), monocyte chemoattractant protein-1 and colony stimulating factor-1. These macrophage-related factors might contribute to inflammation and formation of granulation tissue. OX6(+) macrophages expressing class II molecules of the major histocompatibility complex became predominant in the healing stages (15-26 dpw), indicating important roles for antigen-presenting cells in tissue remodelling. The OX6(+) macrophages were most likely derived from ED1(+) macrophages. The results of this study show that infiltration of phenotypically- and functionally-distinct macrophage populations characterizes different stages of the wound healing process. (C) 2011 Elsevier Ltd. All rights reserved.
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