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Inducible Expression Of The Inflammatory Protein Cap37 In The Epidermis During Wound Healing (pp. 133-148) $25.00
Authors:  Pereira, H. Anne, Kumar, Padmasini and Lerner, Megan R. (University of Oklahoma Health Sciences Center); Brackett, Daniel J. (Veteran’s Affairs Medical Center, Oklahoma City, OK)
Abstract:
CAP37 is a multifunctional protein with important implications in host defense and inflammation. Due to its location and function, CAP37 has traditionally been considered a component of the innate defense system of the host. It is constitutively expressed in the granules of human neutrophils and was first discovered because of its strong antimicrobial activity. Distinct from its effect on bacteria, it is now known that native CAP37 has potent regulatory effects on host cells. It is an effective regulator of monocytes, macrophages, and microglia and also regulates endothelial and smooth muscle cell functions. Since macrophages play a critical role in wound healing we hypothesized that CAP37, a potent and specific chemoattractant for monocytes may contribute to the wound healing process by promoting migration of monocytes. Using a well characterized rat model of wound healing we investigated the expression of CAP37 in sterile wounds (1.5 cm x 1.5 cm) over a 35 day time period. Immunohistochemical analysis demonstrated CAP37 expression not only in the granules of migrating neutrophils as expected, but also in epidermal cells, the sebaceous glands, cells lining the hair follicles, and in endothelial cells lining newly forming capillaries. Expression of the inducible form of CAP37 was first seen at day one following wounding. Skin taken at the time of wounding showed no CAP37 expression in extraneutrophilic sites, indicating that CAP37 was induced as a result of wounding. These novel findings on the inducible expression of CAP37 in response to wounding in cells most likely to come in contact with bacteria such as the epidermal cells of the skin suggest a host defense molecule that could be of great benefit in warding off infection. Additionally, we treated certain wounds with recombinant CAP37 (10 ěg/100 ěl) or saline every 24 hours for 7 days and investigated the influx of monocytes to the wound surface. The administration of recombinant CAP37 to the surface of the wound dramatically affected the migration of monocytes to the wound site. Wounds treated with CAP37 showed significant numbers of monocytes within 24 hours. Whereas, vehicle-treated wounds did not show comparable levels of monocyte migration until day 5. It is our contention, that the inducible forms of CAP37 expressed in epithelial and endothelial cells are involved in host defense through the combined effect of its bactericidal activity and immunomodulatory effects on host cells thereby regulating leukocyte emigration and healing 


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Inducible Expression Of The Inflammatory Protein Cap37 In The Epidermis During Wound Healing (pp. 133-148)