Macrophage dysfunction impairs resolution of inflammation in the wounds of diabetic mice

PloS One
Savita KhannaSashwati Roy

Abstract

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. 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. Taken together, this study presents first evidence demonstrating that diabetic wounds suffer from dysfunctional macrophage efferocytosis resulting in increased apoptot...Continue Reading

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Methods Mentioned

BETA
ELISA
MDA
biopsies
amputations
PCR

Related Concepts

Metazoa
Streptozotocin Diabetes
Inflammation
Macrophage
Skin
Wound Healing
Cytokine
Apoptosis, Intrinsic Pathway
Oxidative Stress
Mouse, Swiss

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