Proliferation of Ly6C+ monocytes/macrophages contributes to their accumulation in mouse skin wounds. Issue 4 (28th November 2019)

• Record Type: Journal Article
• Authors: Pang, Jingbo; Urao, Norifumi; Koh, Timothy J.
• Is Part Of: Journal of leukocyte biology. Volume 107:Issue 4(2020)
• Page Start: 551
• Page End: 560
• Publication Date: 2019-11-28
• Subjects: inflammation -- cell cycle -- IL-1 -- IL-6; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1002/JLB.3HI1119-389RRRR
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract: Monocytes and macrophages (Mo/MΦ) play critical roles in all phases of skin wound healing. The majority of these cells are thought to be recruited from blood Mo; however, the role local proliferation of Mo/MΦ in the wound has not been defined. Therefore, we tested the hypothesis that local proliferation of Mo and/or MΦ contributes to their accumulation during wound healing. Male C57Bl/6 mice ( N = 4–9/group) were subjected to excisional skin wounding. Proliferating Mo/MΦ (F4/80+Ki67+) were observed in wound cryosections, peaking on day 5 post-wounding. Cell cycle analysis on cells isolated from skin tissue revealed that wounding increased both the number and percentage of inflammatory Ly6C+F4/80lo/− Mo/MΦ in the S/G2/M phases, peaking on day 6 post-wounding. In contrast, more mature Ly6C-F4/80+ cells were found predominantly in the G0 phase with less than 1% cells in S/G2/M phase following injury. In peripheral blood, Mo were very rarely found in the S/G2/M phase, suggesting that the wound environment triggered the Ly6C+F4/80lo/− Mo proliferative response. Furthermore, injury induced several potential regulators of proliferation in wounds, including IL-1β and IL-6, and wound Mo/MΦ expressed surface receptors for these cytokines. However, wound Mo/MΦ proliferation was not altered in IL-1R1 knockout (KO) or IL-6 KO mice. In summary, our findings indicate that proliferation contributes to Mo/MΦ accumulation in wounds and, contrary to findings in other pathophysiologic conditions, Ly6C+/F4/80lo/− Mo/MΦ proliferate during skin wound healing whereas mature Ly6C−F4/80+ MΦ do not.