Work

The matricellular protein CCN1 mediates neutrophil efferocytosis in cutaneous wound healing

Year: 2015

Type: article

Abstract: Neutrophil infiltration constitutes the first step in wound healing, although their timely clearance by macrophage engulfment, or efferocytosis, is critical for efficient tissue repair. However, the specific mechanism for neutrophil clearance in wound healing remains undefined. Here we uncover a key role for CCN1 in neutrophil efferocytosis by acting as a bridging molecule that binds phosphatidylserine, the ‘eat-me’ signal on apoptotic cells and integrins αvβ3/αvβ5 in macrophages to trigger efferocytosis. Both knockin mice expressing a mutant CCN1 that is unable to bind αvβ3/αvβ5 and mice with Ccn1 knockdown are defective in neutrophil efferocytosis, resulting in exuberant neutrophil accumulation and delayed healing. Treatment of wounds with CCN1 accelerates neutrophil clearance in both Ccn1 knockin mice and diabetic Leprdb/db mice, which suffer from neutrophil persistence and impaired healing. These findings establish CCN1 as a critical opsonin in skin injury and suggest a therapeutic potential for CCN1 in certain types of non-healing wounds. Neutrophils are the first line of response to injury but their persistence can inhibit the resolution phase of tissue repair. Here the authors show that an extracellular matrix protein promotes neutrophil clearance by macrophages, serving as a bridge between the two cell types and speeding up tissue repair.

Source: Nature Communications

DOI: 10.1038/ncomms8386

Authors: Joon-Il Jun, Ki-Hyun Kim, Lester F. Lau

Institution: University of Illinois Chicago

Language: English

Topic: Wound Healing and Treatments

Subfield: Surgery

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $6,990