title: Substance P levels and neutral endopeptidase activity in acute burn wounds and hypertrophic scar.
abstract: BACKGROUND
  Substance P, a cutaneous neuroinflammatory mediator released from peripheral nerves, plays a role in responses to injury. Neutral endopeptidase is a cell membrane-bound metallopeptidase enzyme that regulates substance P activity. The question of substance P involvement in hypertrophic scar development has been based on observations that hypertrophic scars have increased numbers of nerves. The authors hypothesized that hypertrophic scar has greater substance P levels and decreased neutral endopeptidase activity compared with uninjured skin and acute partial-thickness burns, which may contribute to an exuberant response to injury.
  
  
  METHODS
  The authors obtained small skin samples of deep partial-thickness burns (n = 7; postburn days 7 to 78) and uninjured skin (n = 14) from patients (eight male patients and six female patients; 2 to 71 years old) undergoing burn wound excision. Hypertrophic scar samples were obtained from six patients (three male patients and three female patients; 8 to 47 years old) undergoing surgical excision 13 to 64 months after burn injury. Protein concentrations were determined using a bicinchoninic acid assay. Substance P concentration was determined by means of indirect enzyme-linked immunosorbent assay. Neutral endopeptidase activity was measured using an enzymatic assay that quantifies a fluorescent degradation product, methoxy-2-naphthylamine (MNA). Substance P and neutral endopeptidase data were standardized to sample weight.
  
  
  RESULTS
  Substance P levels were greater in hypertrophic scar (3506 pg/g) compared with uninjured skin (1698 pg/g; p < 0.03) and burned skin (958 pg/g; p < 0.01). Hypertrophic scar samples had decreased neutral endopeptidase enzyme activity (8.8 pM MNA/hour/microg) compared with normal skin (16.3 pM MNA/hour/microg; p < 0.05). Acute burn wounds (27.9 pM MNA/hour/microg) demonstrated increased neutral endopeptidase enzyme activity (p < 0.05).
  
  
  CONCLUSIONS
  Increased substance P concentration in hypertrophic scar correlates with histologic findings of increased nerve numbers in hypertrophic scar samples. Decreased neutral endopeptidase enzyme activity in hypertrophic scar may contribute to increased available substance P that may result in an exuberant neuroinflammatory response.
authors.affiliation: Department of Surgery and the Division of Plastic and Reconstructive Surgery, University of Washington, Seattle, Wash, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Scott
authors.forename: Pornprom R
authors.initials: PR
authors.lastname: Muangman
authors.forename: Richard N
authors.initials: RN
authors.lastname: Tamura
authors.forename: Kathy Q
authors.initials: KQ
authors.lastname: Zhu
authors.forename: Zhi
authors.initials: Z
authors.lastname: Liang
authors.forename: Joanne
authors.initials: J
authors.lastname: Anthony
authors.forename: Loren H
authors.initials: LH
authors.lastname: Engrav
authors.forename: Nicole S
authors.initials: NS
authors.lastname: Gibran
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002056:Burns / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D017439:Cicatrix, Hypertrophic / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011933:Reagent Kits, Diagnostic; D013373:Substance P / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology
chemical_list: D011933:Reagent Kits, Diagnostic; D013373:Substance P; D010450:Endopeptidases