COMPLEMENT-MEDIATED ADIPOCYTE LYSIS BY NEPHRITIC FACTOR SERA

Recent data indicate a previously unsuspected link between the complem ent system and adipocyte biology. Murine adipocytes produce key compon ents of the alternative pathway of complement and are able to activate this pathway. This suggested to us an explanation for adipose tissue loss in partial lipodystrophy, a rare human condition usually associat ed with the immunoglobulin G (IgG) autoantibody nephritic factor (NeF) which leads to enhanced alternative pathway activation in vivo. We hy pothesized that in the presence of NeF, there is dysregulated compleme nt activation at the membrane of the adipocyte, leading to adipocyte l ysis. Here we show that adipocytes explanted from rat epididymal fat p ads are lysed by NeF-containing sera but not by control sera. A simila r pattern is seen with IgG fractions of these sera. Adipocyte lysis in the presence of NeF is associated with the generation of fluid-phase terminal complement complexes, the level of which correlates closely w ith the level of lactate dehydrogenase, a marker of cell lysis. Lysis is abolished by ethylenediaminetetraacetic acid, which chelates divale nt cations and prevents complement activation, and reduced by an antib ody to factor D, a key component of the alternative pathway. These dat a provide an explanation for the previously obscure link between NeF a nd fat cell damage.