The terminal complement complex is generated in chronic leg ulcers in the absence of protectin (CD59)

Loss of membrane complement regulators accompanied by complement activation is suggested to be involved in the pathophysiological processes leading to tissue damage in myocardial ischaemia. In the present study we have invest igated whether the same phenomenon may occur in ischaemic and/or venous hyp ertension leg ulcers. The deposition of complement, plasma complement regul ators and expression of membrane regulators were detected by immunohistoche mical methods, including immunofluorescence with antibodies against C3d, th e terminal complement complex (TCC), vitronectin, clusterin, decay-accelera ting factor (CD55) and protectin (CD59). Eleven frozen biopsies from ischae mic leg ulcers, 10 biopsies from venous hypertension leg ulcers, and 10 bio psies from normal skin were studied. In 9 of 11 ischaemic and in 5 of 10 ve nous hypertension leg ulcers, marked staining for TCC was found around the capillaries, most often at the ulcer margin. No TCC staining was found in n ormal skin. Staining for TCC was always accompanied by staining for cluster in and vitronectin and C3d. In normal skin, CD59 was found on the elastic f ibers in the dermis, on the muscle coat, the Schwann sheath and acinar cell s. Semiquantitative measurement of CD59 showed marked increased staining in tensity in the endothelium in venous hypertension ulcers and diminished int ensity in ischaemic ulcers compared to normal skin. No such difference coul d be observed for CD55. When TCC was positive in the capillary walls, weak or no staining for CD59 was found. A significantly higher ratio of TCC/CD59 was found in the ischaemic compared to venous ulcers (p=0.018). This was d ue to a marked difference between the ulcer margins (p=0.013). Localized ar eas in the venous ulcers had the same pattern as that seen in the ischaemic ulcers. Our results suggest that loss of CD59 may enhance deposition of TC C and that complement-dependent inflammation may be an important factor in the tissue-damaging processes seen in chronic leg ulcers.