5-carboxytetramethylrhodamine-succinimidyl-ester and Proteinuria

Mice lacking the membrane tyrosine kinase c-mer have been shown to have altered macro-phage cytokine production and defective phagocytosis of apoptotic cells despite normal phagocytosis of other particles. We show here that c-mer-deficient mice have impaired clearance of infused apoptotic cells and that they develop progressive lupus-like autoimmunity, with antibodies to chromatin, DNA, and IgG. The autoimmunity appears to be driven by endogenous antigens, with little polyclonal B cell activation. These mice should be an excellent model for studying the role of apoptotic debris as an immunogenic stimulus for systemic autoimmunity.

Topics: Animals; Apoptosis; Autoantibodies; Autoimmunity; B-Lymphocytes; c-Mer Tyrosine Kinase; Cardiolipins; Chromatin; Disease Models, Animal; DNA; Female; Fluorescent Dyes; Glomerular Mesangium; Immunoglobulin G; Lupus Erythematosus, Systemic; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Phagocytosis; Protein-Tyrosine Kinases; Proteinuria; Proto-Oncogene Proteins; Receptor Protein-Tyrosine Kinases; Rheumatoid Factor; Rhodamines