title: Skin-infiltrating neutrophils following exposure to solar-simulated radiation could play an important role in photoageing of human skin.
abstract: BACKGROUND
  The pathophysiology of photoageing of the skin has been studied extensively. Matrix metalloproteinases (MMPs) originating from keratinocytes and fibroblasts are thought to play a primary role in this process. Although neutrophils are potent producers of a wide array of proteolytic substances and are present in sunburned skin, their contribution to the pathophysiology of photoageing has been described only in murine studies.
  
  
  OBJECTIVE
  To determine the role of neutrophils in photoageing of human skin.
  
  
  METHODS
  Healthy white-skinned volunteers were recruited and their sun-protected buttock skin was exposed to solar-simulated radiation (SSR) in dose-response and time-course studies. Punch biopsies were taken and the influx of neutrophils and the expression of neutrophil elastase and MMPs was studied using immunohistochemical techniques and in situ zymography.
  
  
  RESULTS
  Neutrophil elastase and MMPs were detected only in skin irradiated with erythemogenic doses (> or = 1 minimal erythema doses) of SSR. Immunohistochemical double staining demonstrated neutrophils to be the major source of MMP-1, MMP-8 and MMP-9. In situ zymography showed elastase, collagenase and gelatinase enzyme activity in those cells.
  
  
  CONCLUSIONS
  Our study suggests that neutrophils participate in the process of photoageing of human skin as they infiltrate the skin and release enzymatically active elastase (neutrophil elastase), collagenase (MMP-1) and gelatinase (MMP-9).
authors.affiliation: Department of Dermatology, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Rijken
authors.forename: R C M
authors.initials: RC
authors.lastname: Kiekens
authors.forename: P L B
authors.initials: PL
authors.lastname: Bruijnzeel
mesh_terms: D000328:Adult; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D019272:Leukocyte Elastase / Q000378:metabolism; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000528:radiation effects*; D009504:Neutrophils / Q000502:physiology / Q000528:radiation effects; D012867:Skin / Q000201:enzymology / Q000473:pathology / Q000528:radiation effects*; D015595:Skin Aging / Q000473:pathology* / Q000528:radiation effects; D013472:Sunlight
chemical_list: D019272:Leukocyte Elastase; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1