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Original Article
September 1998

Augmented Inflammatory Responses and Altered Wound Healing in Cathepsin G–Deficient Mice

Author Affiliations

From the Division of Plastic and Reconstructive Surgery, Northwestern University Medical School, Chicago, Ill (Drs Abbott, Corral, Lin, and Mustoe); and the Department of Internal Medicine and Genetics Division of Bone Marrow Transplantation and Stem Cell Biology, Washington University School of Medicine, St Louis, Mo (Drs MacIvor and Ley).

Arch Surg. 1998;133(9):1002-1006. doi:10.1001/archsurg.133.9.1002
Abstract

Background  Cathepsin G is a neutral serine proteinase that exists primarily in azurophilic granules of neutrophils, but also as a proteolytically active membrane-bound form. While the specificity and many in vitro biological activities have been described for cathepsin G, little is known about the role of this enzyme in neutrophil function in vivo, particularly as it applies to the wound-healing process.

Objective  To determine the role of cathepsin G in cutaneous tissue repair by examination of full-thickness incisional wound healing in mice with a null mutation for cathepsin G.

Methods  Paired, full-thickness linear incisions were made on the backs of cathepsin G +/+ and cathepsin G −/− mice, and wound tissue was harvested at days 1, 2, 3, 5, 7, 10, and 14 after wounding. Neutrophil influx, myeloperoxidase activity, and migration were examined using light microscopy, the myeloperoxidase assay, and modified Boyden chamber technique, respectively. Wound-breaking strength was measured using tensiometry.

Results  The absence of cathepsin G led to a 42% decrease in wound-breaking strength at day 7 after wounding (n=28; P<.002), which returned to the level of control mice by day 10 after wounding. Wound tissue sections in mice lacking cathepsin G also showed a 26% increase in neutrophil myeloperoxidase activity (n=12; P=.001) and an 18% increase in neutrophil influx (n=14; P=.002) at day 3 after wounding. Wound fluid collected on day 5 after wounding from cathepsin G–deficient mice attracted 58% more neutrophils than wound fluid collected from control mice (n=4; P<.05).

Conclusions  Neutrophil cathepsin G is important during the early inflammatory stage of wound healing. Cathepsin G may be involved in processing 1 (or more) soluble mediator(s) in the wound milieu that is responsible for neutrophil chemotaxis. Our findings suggest that tight regulation of inflammation is necessary to prevent impaired healing during early tissue repair.

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