963-19 Evidence for Complement Activation by Smooth Muscle Cells in Lesions of Advanced Pulmonary Hypertension (PH)

Abstract

In PH and other vascular obstructive diseases, the mediators of intimal hyperplasia of arteries have been extensively studied. Little attention has been given to the pathogenesis of the more advanced pulmonary vascular lesions, such as fibrinoid necrosis and plexiform lesions. Recently, it was shown that the membrane attack complex of the complement (MAC) plays a role in pathologic processes chracterized by cell proliferation, including atherosclerosis. To contribute to the understanding of the development of the arterial obstructive lesions in PH, we studied the expression of MAC in lungs from 8 patients presenting advanced vascular disease: five with primary PH, two with PH secondary to Schistosomiasis and one secondary to a congenital heart defect (mean age 20; median 17.5 years), We characterized immunohistochemically the proliferative vascular lesions using antibodies that recognize the active form of MAC, α -actin and Factor VIII, in paraffin embedded tissue. The intimal lesions, including plexiform lesions, contained predominantly α -actin positive smooth muscle cells (SMC). Factor VIII strongly labelled the endothelial cells of arteries, including the vascular spaces within plexiform lesions. All 8 cases exhibited positive MAC reaction (mild to moderate) in the medial layer of arteries but not of veins, staining individual SMC and also lining the internal and/or external elastic membranes. MAC was constantly negative in the SMC of the plexiform lesions and in endothelial cells. In only 2 of 8 cases was MAC expressed (weakly) in intimal lesions. MAC was also positive focally in fibrinoid necrosis. We conclude that SMC are the main constituents of the intimal and plexiform lesions, and that MAC is always present in the medial SMC. Since MAC is known to induce cell proliferation, our findings may suggest that it participates in the pathogenesis of obstructive lesions in human PH, and that the fibrinoid necrosis of the arterial wall could be related to a complement attack which extends beyond the sublytic stage.