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

Allhorn, MariaLund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine (author)

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.

Lundqvist, KatarinaLund University,Lunds universitet,Dermatologi och venereologi, Lund,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Dermatology and Venereology (Lund),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)derm-klu (author)
Schmidtchen, ArturLund University,Lunds universitet,Dermatologi och venereologi, Lund,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Dermatology and Venereology (Lund),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)derm-asc (author)
Åkerström, BoLund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)medk-bak (author)
InfektionsmedicinSektion III (creator_code:org_t)

In:Journal of Investigative Dermatology: Elsevier BV121:3, s. 640-6461523-17470022-202X

By the author/editor: Allhorn, Maria; Lundqvist, Katar ...; Schmidtchen, Art ...; Åkerström, Bo

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Dermatology and ...

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.