Macrophage dysfunction impairs resolution of inflammation in the wounds of diabetic mice.
Savita Khanna,Sabyasachi Biswas,Yingli Shang,Eric Collard,Ali Azad,Courtney Y. Kauh,Vineet Bhasker,Gayle M. Gordillo,Chandan K. Sen,Sashwati Roy +9 more
Reads0
Chats0
TLDR
First evidence is presented demonstrating that diabetic wounds suffer from dysfunctional macrophage efferocytosis resulting in increased apoptotic cell burden at the wound site, which prolongs the inflammatory phase and complicates wound healing.Abstract:
Background Chronic inflammation is a characteristic feature of diabetic cutaneous wounds. We sought to delineate novel mechanisms involved in the impairment of resolution of inflammation in diabetic cutaneous wounds. At the wound-site, efficient dead cell clearance (efferocytosis) is a pre-requisite for the timely resolution of inflammation and successful healing. Methodology/Principal Findings Macrophages isolated from wounds of diabetic mice showed significant impairment in efferocytosis. Impaired efferocytosis was associated with significantly higher burden of apoptotic cells in wound tissue as well as higher expression of pro-inflammatory and lower expression of anti-inflammatory cytokines. Observations related to apoptotic cell load at the wound site in mice were validated in the wound tissue of diabetic and non-diabetic patients. Forced Fas ligand driven elevation of apoptotic cell burden at the wound site augmented pro-inflammatory and attenuated anti-inflammatory cytokine response. Furthermore, successful efferocytosis switched wound macrophages from pro-inflammatory to an anti-inflammatory mode. Conclusions/Significance Taken together, this study presents first evidence demonstrating that diabetic wounds suffer from dysfunctional macrophage efferocytosis resulting in increased apoptotic cell burden at the wound site. This burden, in turn, prolongs the inflammatory phase and complicates wound healing.read more
Citations
More filters
Journal ArticleDOI
Inflammation and wound healing: the role of the macrophage.
Timothy J. Koh,Luisa A. DiPietro +1 more
TL;DR: The macrophage continues to be an attractive therapeutic target, both to reduce fibrosis and scarring, and to improve healing of chronic wounds, as a result of advances in the understanding of this multifunctional cell.
Journal ArticleDOI
Wound Healing: A Cellular Perspective.
TL;DR: It is shown that changes in the microenvironment including alterations in mechanical forces, oxygen levels, chemokines, extracellular matrix and growth factor synthesis directly impact cellular recruitment and activation, leading to impaired states of wound healing.
Journal ArticleDOI
Transition from inflammation to proliferation: a critical step during wound healing
TL;DR: This review summarizes mechanisms regulating the inflammation–proliferation transition at cellular and molecular levels and proposes that identification of such mechanisms will reveal promising targets for development of more effective therapies.
Journal ArticleDOI
The Role of Macrophages in Acute and Chronic Wound Healing and Interventions to Promote Pro-wound Healing Phenotypes.
TL;DR: The physiology of monocytes and macrophages in acute wound healing and the different phenotypes described in the literature for both in vitro and in vivo models are discussed.
Journal ArticleDOI
Skin Wound Healing: An Update on the Current Knowledge and Concepts.
TL;DR: Although wound healing mechanisms and specific cell functions in wound repair have been delineated in part, many underlying pathophysiological processes are still unknown and redundancy is high and other cells or mediators can adopt functions or signaling without major complications.
References
More filters
Journal ArticleDOI
Obesity is associated with macrophage accumulation in adipose tissue
Stuart P. Weisberg,Daniel McCann,Manisha Desai,Michael Rosenbaum,Rudolph L. Leibel,Anthony W. Ferrante +5 more
TL;DR: Transcript expression in perigonadal adipose tissue from groups of mice in which adiposity varied due to sex, diet, and the obesity-related mutations agouti (Ay) and obese (Lepob) found that the expression of 1,304 transcripts correlated significantly with body mass.
Journal ArticleDOI
Biochemistry and molecular cell biology of diabetic complications
TL;DR: This integrating paradigm provides a new conceptual framework for future research and drug discovery in diabetes-specific microvascular disease and seems to reflect a single hyperglycaemia-induced process of overproduction of superoxide by the mitochondrial electron-transport chain.
Journal ArticleDOI
Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes.
TL;DR: This review provides a comprehensive summary on the chemical properties of 4-hydroxyalkenals and malonaldehyde, the mechanisms of their formation and their occurrence in biological systems and methods for their determination, as well as the many types of biological activities described so far.
Journal ArticleDOI
Interleukin-10 and the interleukin-10 receptor.
TL;DR: Findings that have advanced the understanding of IL-10 and its receptor are highlighted, as well as its in vivo function in health and disease.
Journal ArticleDOI
Cutaneous wound healing.
TL;DR: The primary goals of the treatment of wounds are rapid wound closure and a functional and aesthetically satisfactory scar.