ABSTRACT
PROTECTIVE FUNCTIONS ARE LINKED Colocalization of Defensive Functions Virtually all epidermal functions (with the exception of vitamin D production) can be considered protective and, perhaps more specifically, defensive. Most of these critical protective functions reside in the stratum corneum (SC) (Table 1) (1,2). Yet, as will be discussed below, many individual functions are linked structurally, biochemically, or by common regulatory mechanisms to one or more of the other defensive functions of the SC (Table 2). The structural organization of the SC into a two-compartment system of corneocytes embedded in a lipid matrix further underlies the localization of defensive functions to either the extracellular or cytosolic compartments (Table 1). It is the lamellar body (LB) secretory system that dictates several functions that reside in the SC interstices (Fig. 1), because in addition to secreting lipids, LB delivers hydrolytic enzymes that process lipid precursors into their respective products and at least one serine protease and a variety of glycosidases with uncertain substrates (see chap. 16) (3,4), and orchestrates desquamation (see chap. 11) (5). LB secretes not only lipids and enzymes, but also certain structural proteins, enzyme inhibitors, and antimicrobial peptides to extracellular domains. These include (i) corneodesmosin (6), a novel protein of the outer epidermis that coats the external face of corneodesmosomes, rendering these junctions resistant to premature proteolysis (see chap. 11); (ii) at least two antimicrobial peptide, human b-defensin 2 (hBD2) and the cathelicidin product LL-37 (see chaps. 2 and 22); (iii) and at least three protease inhibitors, elafin (SKALP), cystatin C/K, and the lymphoepithelial kazal-type inhibitor (LEKTI) (see chap. 16).
