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.