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. 2002 Jul 1;196(1):135-40.
doi: 10.1084/jem.20012094.

Delayed apoptotic cell clearance and lupus-like autoimmunity in mice lacking the c-mer membrane tyrosine kinase

Philip L Cohen  1 , Roberto Caricchio, Valsamma Abraham, Todd D Camenisch, J Charles Jennette, Robert A S Roubey, H Shelton Earp, Glenn Matsushima, Elizabeth A Reap
Affiliations

Delayed apoptotic cell clearance and lupus-like autoimmunity in mice lacking the c-mer membrane tyrosine kinase

Philip L Cohen et al. J Exp Med. .

Abstract

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.

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Figures

Figure 1.
Figure 1.
Detection of apoptotic cells after infusion. 75–100 × 106 TAMRA-labeled apoptotic cells were given IV to mer kd or B6 mice and spleens removed 14 h later and analyzed using flow cytometry. Apoptotic cells were identified by gating using forward and side scattering and are denoted in the middle and bottom boxes (early and late apoptotic cells). Red fluorescence of these populations is shown on the right, and depicts TAMRA-labeled cells. This figure is representative of three experiments. In each experiment at least two mice per group were used. Mean ± SD of all three experiments is shown.
Figure 2.
Figure 2.
Anti-chromatin in mer kd and control mice. Mice aged from 2–10 mo were bled and serum analyzed by ELISA for anti-chromatin. Results indicated ng/ml of specific antibody. Similar results were observed in two other cohorts of mice. Asterisks indicate P < 0.05 when mer kd mice were compared with B6 mice.
Figure 3.
Figure 3.
Anti-ssDNA in mer kd and control mice. The same cohort of mice shown in Fig. 2 was tested for anti-ssDNA by ELISA. Results are reported as ng/ml of specific antibody.
Figure 4.
Figure 4.
Rheumatoid factor in mer kd and control mice. The same sera were tested for IgM antibody to IgG2b by ELISA. Results are representative of three experiments.
Figure 5.
Figure 5.
Total IgG in mer kd and control mice. Total IgG was measured by ELISA.
See this image and copyright information in PMC

References

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