Macrophage-Mediated Inflammation in Normal and Diabetic Wound Healing

Abstract

The healing of cutaneous wounds is dependent on the progression through distinct, yet overlapping phases of wound healing, including hemostasis, inflammation, proliferation, and resolution/remodeling. The failure of these phases to occur in a timely, progressive fashion promotes pathologic wound healing. The macrophage (MΦ) has been demonstrated to play a critical role in the inflammatory phase of tissue repair, where its dynamic plasticity allows this cell to mediate both tissue-destructive and -reparative functions. The ability to understand and control both the initiation and the resolution of inflammation is critical for treating pathologic wound healing. There are now a host of studies demonstrating that metabolic and epigenetic regulation of gene transcription can influence MΦ plasticity in wounds. In this review, we highlight the molecular and epigenetic factors that influence MΦ polarization in both physiologic and pathologic wound healing, with particular attention to diabetic wounds.

Wound healing can be improved by (—)‐epigallocatechin gallate through targeting Notch in streptozotocin‐induced diabetic mice

“…Emerging evidence suggests that macrophage dysfunction is a component of the pathogenesis of nonhealing and poorly healing wounds (25,27). In addition, extensive research has reported that macrophage accumulation is observed in patients with diabetes and plays an important role in wound healing (13,28). In individuals with type 2 diabetes, a study sustained the notion that inflammasome activity in macrophages impairs wound healing and a significantly higher number of macrophages are present in the edge of both types of chronic ulcer (diabetic wounds and venous ulcers) (29).…”

Pseudomonas aeruginosa infection alters the macrophage phenotype switching process during wound healing in diabetic mice

“…A group of new strategies have been developed to promote the healing of these wounds, although the outcome is still not satisfactory (Alavi et al, 2014). Macrophage polarization plays critical roles in the wound healing process (Ferrante and Leibovich, 2012;Novak and Koh, 2013;Boniakowski et al, 2017). Therefore, clarifying the events of macrophage phenotype switching in bacterium-infected diabetic wounds is helpful for understanding the etiology of non-healing diabetic foot ulcers.…”

Proliferation of Ly6C+ monocytes/macrophages contributes to their accumulation in mouse skin wounds

“…The majority of Mo/MΦ that accumulate in skin wounds are thought to derive from circulating blood Mo in mice . Mo are produced in bone marrow by sequential differentiation from hematopoietic stem cells, under the control of a variety of growth factors and transcription factors .…”

“…Tissue damage also results in increased bone marrow monopoiesis, which helps to supply Mo for tissue repair and to repopulate bone marrow and blood stores . Although most Mo/MΦ in skin wounds are thought to be derived from bone marrow Mo, a small population of skin resident MΦ also likely act as first responders upon wounding, contributing to the initiation of inflammation …”

“…13 Although most Mo/MΦ in skin wounds are thought to be derived from bone marrow Mo, a small population of skin resident MΦ also likely act as first responders upon wounding, contributing to the initiation of inflammation. 8 In addition to the recruitment of blood Mo, cell proliferation may contribute to tissue Mo/MΦ accumulation under certain conditions. [14][15][16][17][18] For example, Jenkins et al 17 have demonstrated that both pleural resident MΦ and MΦ recruited to the peritoneal cavity can proliferate during TH2-related pathologies such as L. sigmodontis and Brugia malayi infection.…”