Complement-mediated adipocyte lysis by nephritic factor sera.
Recent data indicate a previously unsuspected link between the complement system and adipocyte biology. Murine adipocytes produce key components 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 associated with the immunoglobulin G(IgG) autoantibody nephritic factor (NeF) which leads to enhanced alternative pathway activation in vivo. We hypothesized that in the presence of NeF, there is dysregulated complement activation at the membrane of the adipocyte, leading to adipocyte lysis. Here we show that adipocytes explanted from rat epididymal fat pads are lysed by NeF-containing sera but not by control sera. A similar 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 with the level of lactate dehydrogenase, a marker of cell lysis. Lysis is abolished by ethylenediaminetetraacetic acid, which chelates divalent cations and prevents complement activation, and reduced by an antibody to factor D, a key component of the alternative pathway. These data provide an explanation for the previously obscure link between NeF and fat cell damage.
Department of Medicine, University of Cambridge, UK.
P W
PW
Mathieson
R
R
Würzner
D B
DB
Oliveria
P J
PJ
Lachmann
D K
DK
Peters
D000273:Adipose Tissue / Q000473:pathology*; D000818:Animals; D003178:Complement C3 Nephritic Factor / Q000502:physiology*; D015938:Complement Membrane Attack Complex / Q000032:analysis; D003165:Complement System Proteins / Q000502:physiology*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008060:Lipodystrophy / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN
D003178:Complement C3 Nephritic Factor; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins; D007770:L-Lactate Dehydrogenase