This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (25)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Surgery, Other  • Alert me on articles by topic  Social Bookmarking   What's this?

Robert E. Abbott, MD; Claudio J. Corral, MD; Debra Marie MacIvor, PhD; Xuanhan Lin, DDS, MS; Timothy J. Ley, MD; Thomas A. Mustoe, MD

Arch Surg. 1998;133:1002-1006.

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.

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).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

The Sulfate Groups of Chondroitin Sulfate- and Heparan Sulfate-containing Proteoglycans in Neutrophil Plasma Membranes Are Novel Binding Sites for Human Leukocyte Elastase and Cathepsin G
Campbell and Owen
J. Biol. Chem. 2007;282:14645-14654.
ABSTRACT | FULL TEXT  

Identification of Neutrophil Granule Protein Cathepsin G as a Novel Chemotactic Agonist for the G Protein-Coupled Formyl Peptide Receptor
Sun et al.
J. Immunol. 2004;173:428-436.
ABSTRACT | FULL TEXT  

Cathepsin G Activates Protease-activated Receptor-4 in Human Platelets
Sambrano et al.
J. Biol. Chem. 2000;275:6819-6823.
ABSTRACT | FULL TEXT  

Normal Neutrophil Function in Cathepsin G-Deficient Mice
MacIvor et al.
Blood 1999;94:4282-4293.
ABSTRACT | FULL TEXT  

Dipeptidyl peptidase I is required for the processing and activation of granzymes A and B in vivo
Pham and Ley
Proc. Natl. Acad. Sci. USA 1999;96:8627-8632.
ABSTRACT | FULL TEXT