THE ROLE OF VASCULAR SMOOTH-MUSCLE CELLS IN EXPERIMENTAL AUTOIMMUNE VASCULITIS .1. THE INITIATION OF DELAYED-TYPE HYPERSENSITIVITY ANGIITIS

Abstract

The destruction of vascular smooth muscle cells (VSMC) in autoimmune arteritis is a poorly understood phenomenon. For evaluation of the cellular interactions that may contribute to vasculitis, the immunobiology of VSMC and lymphocytes [from mice] was explored in vitro. Primary VSMC cultures were established and the interaction of these cells (from normal or autoimmune mice) with lymphocytes was then assessed. Specifically, splenocytes [SP] from MRL/lpr or C3H mice were cocultivated with MRL/lpr or C3H VSMC. Massive mononuclear cell clusters from normal and autoimmune mice enveloped MRL/lpr VSMC, which culminated in the detachment of MRL/lpr VSMC from the culture plate. In contrast, the interaction of SP from either normal or autoimmune mice did not encompass or destroy normal VSMC. Further investigation indicated that MRL/lpr, but not C3H, VSMC spontaneously expressed Ia and released Il-1 like factor(s), which may be at least 2 mechanisms by which MRL/lpr VSMC stimulate the in vitro mononuclear cell influx. A novel mechanism for the induction of mononuclear cell autoimmune vasculitis was proposed. VSMC derived from autoimmune mice may stimulate a mononuclear inflammatory cell phlogistic response which culminates in VSMC autodestruction.