Thrombospondin (TSP) is a newly described protein of the extracellular matrix (ECM). The purpose of this project is to investigate its function in the epidermis. The initial approach to this problem will be via an in vitro model. Pure human keratinocyte cultures in a defined, serum-free medium will be used to investigate the effects of numerous variables (cellular, culture, substrate, external mediators) on the synthesis and distribution of TSP by keratinocytes. Immunohistochemical techniques at both the light and electron microscopic levels will be used to investigate the distribution of TSP and its spacial relationship to other ECM proteins in normal skin, healing wounds, and some inflammatory and bullous skin diseases. Through these studies the biological function of TSP in the epidermis should be illuminated.