HIghlights of the IID. Part 3: How Melanin Is Good For The Skin Barrier

In previous work, we demonstrated that the skin of darkly-pigmented people possesses a tighter, more competent barrier to water leakage than does the skin of lightly-pigmented individuals.  Although we could attribute this to the much more acidic (lower pH) skin surface in individuals with dark pigmentation, just how either melanin or its parent cell, the melanocyte, confers these benefits was unknown.

For the studies reported here, we took advantage of two closely related strains of hairless mice – one that is darkly pigmented (hrs/J), and a a closely-related strain that is pink or albino (hr/hr). As expected, the barrier was better in the pigmented mice, and these darker mice, like their more heavily pigmented human counterparts, also exhibited a more acidic stratum corneum. In the pigmented mice (just as in darkly pigmented human skin), melanin granules persisted out into the stratum corneum, and eventually some of these granules are released into the spaces between the cells of the stratum corneum (corneocytes). 

We were able to show that the pH became much more acidic in the regions of the stratum corneum surrounding these melanin granules.  Moreover, when the permeability barrier was disrupted by either tape stripping or wiping the skin surface with organic solvents, both pigmented and albino mice lost their acidic surface pH. Yet, the pigmented mice recovered their barrier function and their acidic pH much more quickly than did the albinos. This rapid recovery of acidity in the pigmented mice correlated precisely with the extrusion of all their remaining cytosolic melanin granules from the keratinocytes that reside in the the outermost nucleated layer of the epidermis (the granular cell layer).

Thus, the increased acidity of pigmented skin can be attributed to the persistence of highly acidic melanin granules into the outer epidermis, and their eventual release into the extracellular spaces of the stratum corneum.

We also found that pigmented mouse skin is functionally superior in other ways. It displays enhanced synthesis of lipids destined to form the permeability barrier in the stratum corneum. And it exhibits increased production of several proteins critical for corneocyte function, such as filaggrin. Thus, the merits of pigmentation extend beyond just acidification.

Perhaps most importantly, we also observed that the antimicrobial defenses of pigmented mouse skin are superior.  Not only does the more acidic surface of pigmented skin repel colonization by pathogenic microorganisms, it also increases the production of two antimicrobial peptides that can kill pathogens, should they attempt to invade the epidermis. These differences in lipids, structural proteins and antimicrobial protein content imply that melanin-producing cells (‘melanocytes’) augment epidermal metabolism in several important ways. However, what melanocyte-derived factor(s) is (are) responsible for these benefits remain(s) to be identified.

Bottom line: This study represents a step towards understanding how darkly pigmented skin is superior to lightly-pigmented skin, and provides further support for our hypothesis that skin of the ancestors of early man developed dark epidermal pigmentation because it provided a superior barrier to water loss and against infections.