AUGMENTED INFLAMMATORY RESPONSES AND ALTERED WOUND-HEALING IN CATHEPSIN G-DEFICIENT MICE

Background: Cathepsin G is a neutral serine proteinase that exists pri marily in azurophilic granules of neutrophils, but also as a proteolyt ically active membrane-bound form. While the specificity and many in v itro 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 exa mination of full-thickness incisional wound healing in mice with a nul l mutation for cathepsin G. Methods: Paired, full-thickness linear inc isions were made on the backs of cathepsin G +/+ and cathepsin G -/- m ice, and wound tissue was harvested at days 1, 2, 3, 5, 7, 10, and 14 after wounding. Neutrophil influx, myeloperoxidase activity, and migra tion were examined using light microscopy, the myeloperoxidase assay, and modified Boyden chamber technique, respectively. Wound-breaking st rength was measured using tensiometry. Results: The absence of catheps in G led to a 42% decrease in wound-breaking strength at day 7 after w ounding (n = 28; P<.002), which returned to the level of control mice by day 10 after wounding. Wound tissue sections in mice lacking cathep sin G also showed a 26% increase in neutrophil myeloperoxidase activit y (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 aft er wounding from cathepsin G-deficient mice attracted 58% more neutrop hils than wound fluid collected from control mice (n = 4; P<.05). Conc lusions: Neutrophil cathepsin G is important during the early inflamma tory stage of wound healing. Cathepsin G may be involved in processing 1 (or more) soluble mediator(s) in the wound milieu that is responsib le for neutrophil chemotaxis. Our findings suggest that tight regulati on of inflammation is necessary to prevent impaired healing during ear ly tissue repair.