MACROPHAGE TARGETED PHOTODYNAMIC REGULATION OF WOUND HEALING

$24,634P41FY2000RRNIH

University Of California Irvine, Irvine CA

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Abstract

Wound healing processes are coordinated by the diverse activities of cells of the monocyte/macrophage lineage. Macrophage depletion impairs wound healing, while overexpression of macrophage products is associated with chronic chronic inflammatory states. If lightactivatable pharmacologic agents could be selectively targeted to macrophages, clinical conditions resulting from overexpression such as postsurgical adhesions, hypertrophic scarring and the formation of intimal hyperplasia could be surpressed. Similarly, adjusting light dose parameters to provide a stimulatory effect could selectively enhance wound repair processes. To test these hypotheses, photoactivable cytoxins (photosensitizers) coupled to specific receptor ligands have been evaluated for localization in cells found in cutaneous tissue using a non-invasive imaging method, two-photon microscopy, available at the LAMMP facility. Optimal irradiation parameters will be determined in vitro and in vivo by measuring a variety of morphologic and biochemical endpoints.

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