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- Title
S100A8/A9 is an important host defence mediator in neuropathic foot ulcers in patients with type 2 diabetes mellitus.
- Authors
Trøstrup, Hannah; Holstein, Per; Christophersen, Lars; Jørgensen, Bo; Karlsmark, Tonny; Høiby, Niels; Moser, Claus; Ågren, Magnus
- Abstract
Chronic wounds and in particular diabetic foot ulcers (DFUs) are a growing clinical challenge, but the underlying molecular pathophysiological mechanisms are unclear. Recently, we reported reduced levels of the immunomodulating and antimicrobial S100A8/A9 in non-healing venous leg ulcers (VLUs), while another study found increased S100A8/A9 in DFUs. To clarify these apparently contradictory findings, we compared S100A8/A9 as well as an inducer, lipopolysaccharide (LPS) and selected innate immune response mediators in wound fluids from non-healing DFUs and VLUs with healing wounds. Wound fluids were collected from neuropathic DFUs ( n = 6) and VLUs ( n = 9) of median 2-year duration, and split-thickness skin graft donor site wounds ( n = 10) by standardized method. None of the patients had ischaemic extremities or clinically infected wounds. LPS was determined by limulus amoebocyte lysate test, and S100A8/A9, granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-10 and vascular endothelial growth factor (VEGF) by immunospecific quantitative assays. LPS levels were median 8.7 (interquartile range 5.4-21.2) ng/ml in DFUs compared with 121 (22-2000) ng/ml in VLUs. S100A8/A9 was higher ( p = 0.020) in DFUs [718 (634-811) µg/ml] than in VLUs [303 (252-533) µg/ml]. Neither G-CSF nor IL-10 wound fluid levels differed significantly between the chronic wound groups. VEGF levels correlated with LPS ( r = 0.758, p = 0.011, n = 10) and were higher ( p = 0.024) in VLU wound fluids. LPS ( p < 0.0001), S100A8/A9 ( p = 0.005), G-CSF ( p = 0.003), IL-10 ( p = 0.003) and VEGF ( p = 0.005) were increased in chronic wound fluids combined compared with the sterile donor site wound fluids. The protein alterations in the wounds were not reflected in the patients' sera. Low S100A8/A9 levels may contribute to poor wound healing in colonized chronic wounds with striking difference between DFUs and VLUs.
- Subjects
TREATMENT of diabetic foot; PEOPLE with diabetes; CALCIUM-binding proteins; PATHOLOGICAL physiology; IMMUNOREGULATION; CHRONIC wounds &; injuries; NATURAL immunity; THERAPEUTICS
- Publication
Archives of Dermatological Research, 2016, Vol 308, Issue 5, p347
- ISSN
0340-3696
- Publication type
Article
- DOI
10.1007/s00403-016-1646-7