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Heme-Scavenging Role of alpha1-Microglobulin in Chronic Ulcers.

Allhorn, Maria LU ; Lundqvist, Katarina LU ; Schmidtchen, Artur LU and Åkerström, Bo LU (2003) In Journal of Investigative Dermatology 121(3). p.640-646
Abstract
Chronic venous ulcers are characterized by chronic inflammation. Heme and iron, originating from blood cell hemolysis as well as extravascular necrosis, have been implicated as important pathogenic factors due to their promotion of oxidative stress. It was recently reported that the plasma and tissue protein alpha1-microglobulin is involved in heme metabolism. The protein binds heme, and a carboxy-terminally processed form, truncated alpha1-microglobulin, also degrades heme. Here, we show the presence of micromolar levels of heme and free iron in chronic leg ulcer fluids. Micromolar amounts of alpha1-microglobulin was also present in the ulcer fluids and bound to added radiolabeled heme. Truncated alpha1-microglobulin was found in the... (More)
Chronic venous ulcers are characterized by chronic inflammation. Heme and iron, originating from blood cell hemolysis as well as extravascular necrosis, have been implicated as important pathogenic factors due to their promotion of oxidative stress. It was recently reported that the plasma and tissue protein alpha1-microglobulin is involved in heme metabolism. The protein binds heme, and a carboxy-terminally processed form, truncated alpha1-microglobulin, also degrades heme. Here, we show the presence of micromolar levels of heme and free iron in chronic leg ulcer fluids. Micromolar amounts of alpha1-microglobulin was also present in the ulcer fluids and bound to added radiolabeled heme. Truncated alpha1-microglobulin was found in the ulcer fluids and exogenously added alpha1-microglobulin was processed into the truncated alpha1-microglobulin form. Histochemical analysis of chronic wound tissue showed the presence of iron deposits, heme/porphyrins in infiltrating cells basement membranes and fibrin cuffs around vessels, and alpha1-microglobulin ubiquitously distributed but especially abundant in basement membranes around vessels and at fibrin cuffs. Our results suggest that alpha1-microglobulin constitutes a previously unknown defense mechanism against high heme and iron levels during skin wound healing. Excessive heme and iron, which are not buffered by alpha1-microglobulin, may underlie the chronic inflammation in chronic ulcers. (Less)
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organization
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type
Contribution to journal
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published
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in
Journal of Investigative Dermatology
volume
121
issue
3
pages
640 - 646
publisher
Nature Publishing Group
external identifiers
  • wos:000185073800036
  • pmid:12925227
  • scopus:0041333136
ISSN
1523-1747
DOI
language
English
LU publication?
yes
id
102744a2-6381-4e42-a953-f1634f3b3a75 (old id 117266)
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http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=12925227&dopt=Abstract
date added to LUP
2007-07-02 16:42:08
date last changed
2018-05-29 10:57:10
@article{102744a2-6381-4e42-a953-f1634f3b3a75,
  abstract     = {Chronic venous ulcers are characterized by chronic inflammation. Heme and iron, originating from blood cell hemolysis as well as extravascular necrosis, have been implicated as important pathogenic factors due to their promotion of oxidative stress. It was recently reported that the plasma and tissue protein alpha1-microglobulin is involved in heme metabolism. The protein binds heme, and a carboxy-terminally processed form, truncated alpha1-microglobulin, also degrades heme. Here, we show the presence of micromolar levels of heme and free iron in chronic leg ulcer fluids. Micromolar amounts of alpha1-microglobulin was also present in the ulcer fluids and bound to added radiolabeled heme. Truncated alpha1-microglobulin was found in the ulcer fluids and exogenously added alpha1-microglobulin was processed into the truncated alpha1-microglobulin form. Histochemical analysis of chronic wound tissue showed the presence of iron deposits, heme/porphyrins in infiltrating cells basement membranes and fibrin cuffs around vessels, and alpha1-microglobulin ubiquitously distributed but especially abundant in basement membranes around vessels and at fibrin cuffs. Our results suggest that alpha1-microglobulin constitutes a previously unknown defense mechanism against high heme and iron levels during skin wound healing. Excessive heme and iron, which are not buffered by alpha1-microglobulin, may underlie the chronic inflammation in chronic ulcers.},
  author       = {Allhorn, Maria and Lundqvist, Katarina and Schmidtchen, Artur and Åkerström, Bo},
  issn         = {1523-1747},
  language     = {eng},
  number       = {3},
  pages        = {640--646},
  publisher    = {Nature Publishing Group},
  series       = {Journal of Investigative Dermatology},
  title        = {Heme-Scavenging Role of alpha1-Microglobulin in Chronic Ulcers.},
  url          = {http://dx.doi.org/},
  volume       = {121},
  year         = {2003},
}