title: Induction of protoporphyrin IX by aminolaevulinic acid in actinic keratosis, psoriasis and normal skin: preferential porphyrin enrichment in differentiated cells.
abstract: BACKGROUND
  In photodynamic therapy the endogenous photosensitizer protoporphyrin IX (PpIX) is synthesized following topical application of aminolaevulinic acid (ALA). However, different tissues have distinct PpIX-accumulating properties, due to differences in penetration of ALA through the stratum corneum and/or alterations in the haem cycle. Preferential PpIX accumulation has been reported in terminally differentiated cell cultures but ex vivo data are lacking.
  
  
  OBJECTIVE
  To study the intrinsic PpIX-accumulating capabilities of skin explants from lesional and nonlesional skin in psoriasis and actinic keratosis, with normal skin serving as a control, and to study PpIX accumulation in relation to differentiation status in normal skin.
  
  
  METHODS
  Skin explants from patients with psoriasis, actinic keratosis and normal skin were incubated with ALA and PpIX was measured spectrofluorometrically. PpIX was measured in basal (beta1-integrin-positive) and suprabasal (beta1-integrin-negative) keratinocytes in normal skin. In addition, PpIX accumulation was studied in cell cultures at different levels of confluence and after induction of terminal differentiation.
  
  
  RESULTS
  No significant differences in PpIX content were found between the different tissues. However, increased PpIX was found in beta1-integrin-negative compared with beta1-integrin-positive cells. In addition, in subconfluent cell cultures less PpIX was found compared with confluent cell cultures. Induction of terminal differentiation in vitro, however, resulted in less PpIX, which was likely to be related to cell volume.
  
  
  CONCLUSIONS
  As no significant differences in PpIX synthesis could be found between the different tissue types, these data emphasize the importance of the penetration route of ALA through the stratum corneum. Preferential PpIX accumulation observed in suprabasal epidermal keratinocytes and confluent cell cultures points towards a terminal differentiation-specific effect.
authors.affiliation: Department of Dermatology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, the Netherlands. t.smits@derma.umcn.nl
authors.forename: T
authors.initials: T
authors.lastname: Smits
authors.forename: A I M
authors.initials: AI
authors.lastname: van Laarhoven
authors.forename: A
authors.initials: A
authors.lastname: Staassen
authors.forename: P C M
authors.initials: PC
authors.lastname: van de Kerkhof
authors.forename: P E J
authors.initials: PE
authors.lastname: van Erp
authors.forename: M-J P
authors.initials: MJ
authors.lastname: Gerritsen
mesh_terms: D000287:Administration, Topical; D000622:Aminolevulinic Acid / Q000494:pharmacology*; D006801:Humans; D055623:Keratosis, Actinic / Q000188:drug therapy* / Q000628:therapy; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000378:metabolism; D011524:Protoporphyrins / Q000096:biosynthesis*; D011565:Psoriasis / Q000188:drug therapy* / Q000628:therapy; D012869:Skin Absorption; D013050:Spectrometry, Fluorescence
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX