Production of melanocyte-specific antibodies to human melanosomal proteins: expression patterns in normal human skin and in cutaneous pigmented lesions.
Multiple factors affect skin pigmentation, including those that regulate melanocyte and/or keratinocyte function. Such factors, particularly those that operate at the level of the melanosome, are relatively well characterized in mice, but the expression and function of structural and enzymatic proteins in melanocytes in human skin are not as well known. Some years ago, we generated peptide-specific antibodies to murine melanosomal proteins that proved to be instrumental in elucidating melanocyte development and differentiation in mice, but cross-reactivity of those antibodies with the corresponding human proteins often was weak or absent. In an effort to characterize the roles of melanosomal proteins in human skin pigmentation, and to understand the underlying mechanism(s) of abnormal skin pigmentation, we have now generated polyclonal antibodies against the human melanocyte-specific markers, tyrosinase, tyrosinase-related protein (TYRP1), Dopachrome tautomerase (DCT) and Pmel17 (SILV, also known as GP100). We used these antibodies to determine the distribution and function of melanosomal proteins in normal human skin (adult and newborn) and in various cutaneous pigmented lesions, such as intradermal nevi, lentigo simplex, solar lentigines and malignant melanomas. We also examined cytokeratin expression in these same samples to assess keratinocyte distribution and function. Immunohistochemical staining reveals distinct patterns of melanocyte distribution and function in normal skin and in various types of cutaneous pigmented lesions. Those differences in the expression patterns of melanocyte markers provide important clues to the roles of melanocytes in normal and in disrupted skin pigmentation.
Virador
V
V
Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Matsunaga
N
N
Matsunaga
J
J
Valencia
J
J
Oldham
R J
RJ
Kameyama
K
K
Peck
G L
GL
Ferrans
V J
VJ
Vieira
W D
WD
Abdel-Malek
Z A
ZA
Hearing
V J
VJ
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D002478:Cells, Cultured; D005629:Frozen Sections; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D019746:Intramolecular Oxidoreductases / Q000032:analysis / Q000276:immunology; D015603:Keratinocytes / Q000737:chemistry / Q000201:enzymology / Q000276:immunology; D007911:Lentigo / Q000473:pathology*; D008544:Melanocytes / Q000737:chemistry* / Q000201:enzymology / Q000276:immunology*; D008545:Melanoma / Q000473:pathology; D020460:Melanosomes / Q000737:chemistry / Q000201:enzymology / Q000276:immunology; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D014442:Monophenol Monooxygenase / Q000032:analysis / Q000276:immunology; D018330:Nevus, Intradermal / Q000473:pathology; D010088:Oxidoreductases; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D011506:Proteins / Q000032:analysis / Q000276:immunology; D011817:Rabbits; D012867:Skin / Q000737:chemistry* / Q000166:cytology / Q000201:enzymology; D012878:Skin Neoplasms / Q000473:pathology; D012880:Skin Pigmentation; D058951:gp100 Melanoma Antigen
D008562:Membrane Glycoproteins; C548637:PMEL protein, human; D010446:Peptide Fragments; C548642:Pmel protein, mouse; D011506:Proteins; D058951:gp100 Melanoma Antigen; D010088:Oxidoreductases; C489799:TYRP1 protein, human; C064056:tyrosinase-related protein-1; D014442:Monophenol Monooxygenase; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase