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

• Published in: APMIS : acta pathologica, microbiologica et immunologica Scandinavica Vol. 107; no. 7-12; pp. 997 - 1004
• Main Authors: Balslev, Eva, Thomsen, Henrik Klem, Danielsen, Lis, Sheller, Jeanet, Garred, Peter
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.1999; Blackwell
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; CD55 Antigens - metabolism; CD59 Antigens - metabolism; clusterin; Complement Membrane Attack Complex - biosynthesis; Dermatology; Female; Humans; Hypertension - complications; Hypertension - immunology; Immunohistochemistry; Inflammation - immunology; ischaemia; Ischemia - complications; Ischemia - immunology; Leg Ulcer - etiology; Leg Ulcer - immunology; Leg ulcers; Male; Medical sciences; Middle Aged; protectin (CD59 and CD55); terminal complement complex (TCC); Varicose Ulcer - etiology; Varicose Ulcer - immunology; Vascular disorders of the skin; venous hypertension; vitronectin; Human; Skin disease; Pathophysiology; Lower limb; Cardiovascular disease; Vitronectin; Activation; Complement; Inflammation; Terminal; Venous disease; Clusterin; Leg; Venous hypertension; Ulcer; Immune system
• ISSN: 0903-4641; 1600-0463
• DOI: 10.1111/j.1699-0463.1999.tb01502.x

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 investigated whether the same phenomenon may occur in ischaemic and/or venous hypertension leg ulcers. The deposition of complement, plasma complement regulators and expression of membrane regulators were detected by immunohistochemical methods, including immunofluorescence with antibodies against C3d, the terminal complement complex (TCC), vitronectin, clusterin, decay‐accelerating factor (CD55) and protectin (CD59). Eleven frozen biopsies from ischaemic leg ulcers, 10 biopsies from venous hypertension leg ulcers, and 10 biopsies from normal skin were studied. In 9 of 11 ischaemic and in 5 of 10 venous hypertension leg ulcers, marked staining for TCC was found around the capillaries, most often at the ulcer margin. No TCC staining was found in normal skin. Staining for TCC was always accompanied by staining for clusterin and vitronectin and C3d. In normal skin, CD59 was found on the elastic fibers in the dermis, on the muscle coat, the Schwann sheath and acinar cells. Semiquantitative measurement of CD59 showed marked increased staining intensity in the endothelium in venous hypertension ulcers and diminished intensity in ischaemic ulcers compared to normal skin. No such difference could 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 due to a marked difference between the ulcer margins (p=0.013). Localized areas 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 TCC and that complement‐dependent inflammation may be an important factor in the tissue‐damaging processes seen in chronic leg ulcers.