title: S100A8/A9 deficiency in nonhealing venous leg ulcers uncovered by multiplexed antibody microarray profiling.
abstract: BACKGROUND
  Knowledge on the underlying mechanisms for nonhealing chronic wounds is fragmentary.
  
  
  OBJECTIVE
  To increase our understanding of the pathogenesis, the relationship between healing ability and a large panel of proteins was studied using a specially designed wound-healing antibody-based microarray.
  
  
  METHODS
  Wound fluid from nondiabetic patients with nonhealing venous leg ulcers was compared with that from patients with healing open granulating acute wounds. The high-throughput method enabled simultaneous measurement of the relative levels of 48 different proteins representing major categories of wound-healing modulators.
  
  
  RESULTS
  Unexpectedly, several of the examined proteins, including various proinflammatory cytokines, proteinases and antiproteinases, were not significantly (P>0·001) changed in chronic wound fluid. For example, levels of matrix metalloproteinase-9 and one of its substrates type IV collagen were similar in the two groups. The wound fluid samples displayed similar degrees of fragmentation of fibronectin by Western blot analysis and the total fibronectin levels were doubled (P<0·001) in chronic compared with acute wounds. The increased fibronectin originated from α-smooth muscle actin-positive myofibroblasts and not from the circulation. S100A8/A9 was the sole protein that was reduced (P<0·001) in wound fluid from venous ulcers [median 226 μg mL(-1) (interquartile range 213-278)] compared with healing wounds [455 μg mL(-1) (382-504)], probably reflecting a difference in inflammatory cell composition.
  
  
  CONCLUSIONS
  The molecular anomalies in chronic wounds are more subtle than the current paradigm and neither excessive proteinase activity nor deficiencies of examined extracellular matrix proteins, growth factors or angiogenic/angiostatic factors appear to contribute significantly to the nonhealing state of venous leg ulcers.
authors.affiliation: Copenhagen Wound Healing Center, Department of Dermatology, Bispebjerg University Hospital, Bispebjerg Bakke 23, DK-2400 Copenhagen NV, Denmark.
authors.forename: H
authors.initials: H
authors.lastname: Trøstrup
authors.forename: R
authors.initials: R
authors.lastname: Lundquist
authors.forename: L H
authors.initials: LH
authors.lastname: Christensen
authors.forename: L N
authors.initials: LN
authors.lastname: Jorgensen
authors.forename: T
authors.initials: T
authors.lastname: Karlsmark
authors.forename: B B
authors.initials: BB
authors.lastname: Haab
authors.forename: M S
authors.initials: MS
authors.lastname: Agren
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D040501:Calgranulin A / Q000172:deficiency*; D040502:Calgranulin B / Q000378:metabolism*; D002908:Chronic Disease; D004797:Enzyme-Linked Immunosorbent Assay; D005122:Exudates and Transudates / Q000737:chemistry; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D040081:Protein Array Analysis / Q000379:methods; D014647:Varicose Ulcer / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D014945:Wound Healing / Q000502:physiology*; D055815:Young Adult
chemical_list: D040501:Calgranulin A; D040502:Calgranulin B