title: Alterations in the epidermal-dermal melanin axis and factor XIIIa melanophages in senile lentigo and ageing skin.
abstract: BACKGROUND
  Senile lentigo (SL) is a pigmentation disorder that occurs predominantly on the dorsa of the hands, the forearms and the face; its incidence increases with age. Histological hallmarks of SL lesions are hyperpigmentation of the epidermis and elongation of the epidermal rete ridges. Various factors such as alpha-melanocyte-stimulating hormone, endothelin-1 or stem cell factor are involved in the onset and maintenance of the increased pigmentation. Alterations of the dermal compartment have not yet been analysed in detail in SL.
  
  
  OBJECTIVE
  To study the occurrence and distribution of melanin in the dermis from SL and aged skin, biopsies from 12 subjects were morphologically analysed by light and electron microscopy in comparison with unaffected skin.
  
  
  METHODS
  Punch biopsies of SL and adjacent skin from 12 male or female volunteers aged 52-81 years were prepared for light and electron microscopy and samples were analysed by morphological, morphometric, histochemical and immunohistochemical methods.
  
  
  RESULTS
  The epidermis from SL revealed morphological features such as hyperpigmentation of basal keratinocytes and the formation of elongated rete ridges. S100+ melanocytes in the stratum basale were not markedly increased, indicating that the hyperpigmentation is predominantly due to changes in melanin synthesis, distribution or turnover. Quantification of epidermal cells expressing the proliferation marker Ki67 did not show an increase of this parameter in SL, indicating that at least in the established lesion cell proliferation is not enhanced. We further focused on the dermal compartment and observed granulated cells which were more abundant in SL. Electron microscopic and histochemical analysis revealed that the granulation of these cells is based on melanosomes, mostly present in large melanosomal complexes. Immunohistochemistry using antibodies to CD68 and factor XIIIa (FXIIIa) showed these melanophages to be predominantly FXIIIa+ dermal dendrocytes, which were about six times more abundant than CD68+ macrophages.
  
  
  CONCLUSIONS
  In SL an increased number of melanophages was found compared with unaffected skin from the same subject. These melanophages were identified as FXIIIa+ dermal dendrocytes. Possible functional consequences of the massive melanin uptake by dermal dendrocytes are discussed.
authors.affiliation: Institut für Zytobiologie und Zytopathologie, Philipps University of Marburg, Marburg, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Unver
authors.forename: P
authors.initials: P
authors.lastname: Freyschmidt-Paul
authors.forename: S
authors.initials: S
authors.lastname: Hörster
authors.forename: H
authors.initials: H
authors.lastname: Wenck
authors.forename: F
authors.initials: F
authors.lastname: Stäb
authors.forename: T
authors.initials: T
authors.lastname: Blatt
authors.forename: H-P
authors.initials: HP
authors.lastname: Elsässer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001692:Biological Transport; D016022:Case-Control Studies; D020405:Dermis / Q000378:metabolism* / Q000473:pathology; D004817:Epidermis / Q000378:metabolism* / Q000473:pathology; D026122:Factor XIIIa / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007911:Lentigo / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008543:Melanins / Q000032:analysis* / Q000378:metabolism; D020460:Melanosomes / Q000378:metabolism / Q000648:ultrastructure; D008854:Microscopy, Electron; D008875:Middle Aged; D010587:Phagocytosis; D015595:Skin Aging / Q000502:physiology*; D013194:Staining and Labeling
chemical_list: D008543:Melanins; D026122:Factor XIIIa