Ruhr-Universität Bochum

Anatomie und Molekulare Embryologie

Dr. Markus Napirei

Extracellular nucleases, which occur in most body fluids of vertebrates, predominantly belong to a family of Ca2+ and Mg2+ (Mn2+)-dependent endonucleases, which was named by its first identified member, Deoxyribonuclease I (DNase I / DNASE1). So far three further members beside DNASE1 were found: DNASE1-like 1-3 (DNASE1L1-3).
Our group characterizes the physiological functions of these nucleases by employing gene-knockout mouse models. Especially the functions of DNASE1, which is highly expressed by glands lining the gastro- and urogenital tract and DNASE1L3 (DNase γ), which is expressed by macrophages and activated B-cells, are of our major interest. Both nucleases occur in serum of mammals and our experiments hint to their contribution in the suppression of anti-nuclear autoimmunity, which is characteristic for a human disease called Systemic Lupus Erythematosus (SLE). Both enzymes display a complementary substrate specificity – DNASE1 efficiently degrades protein-free DNA whereas DNASE1L3 preferentially hydrolyzes protein-complexed DNA (chromatin) – and appear to cooperate in the destruction of exogenous (microorganisms) and endogenous (primary or secondary necrotic cells) DNA. Impairment of these processes might lead to a prolonged and chronic exposure of the immune system to DNA-antigens leading to an increased probability for the breakdown of self-tolerance towards nuclear antigens. Indeed, SLE is regarded as a multigenetic disease caused by defects which impair the removal of dying cells and cell debris in the context of defects leading to a deregulated and hypersensitive immune system.
In summary, we intend to elucidate the role of extracellular nucleases in the removal of nuclear cell debris released under physiological and pathological conditions (necrosis) and the consequences resulting from an impairment of these processes.

Dr. Markus Napirei

Abteilung für Anatomie und Molekulare Embryologie
Room MA 5/162

Selected Publications

Napirei M., Mannherz H. G. (2009) Molecules involved in recognition and clearance of apoptotic/necrotic cells and cell debris. In Phagocytosis of dying cells: From molecular mechanisms to human disease (Krysko, D. V. and Vandenabeele, P., eds.). pp. 103-145, Springer Verlag

Napirei M., Ludwig S., Mezrhab J., Klöckl T., Mannherz H. G. (2009) Murine serum nucleases-contrasting effects of plasmin and heparin on the activities of DNase1 and DNase1-like 3 (DNase1l3). FEBS J., 276, 1059-1073

Ludwig S., Mannherz H. G., Schmitt S., Schäffer M., Zentgraf H., Napirei M. (2009) Murine serum deoxyribonuclease 1 (Dnase1) activity partly originates from the liver. Int. J. Biochem. Cell Biol., 41, 1079-1093

Jacob M., Mannherz H. G., Napirei M. (2007) Chromatin breakdown by deoxyribonuclease1 promotes acetaminophen-induced liver necrosis: an ultrastructural and histochemical study on male CD-1 mice. Histochem. Cell Biol., 128, 19-33

Napirei M., Gültekin A., Klöckl T., Möröy T., Frostegard J., Mannherz H. G. (2006) Systemic lupus-erythematosus: Deoxyribonuclease 1 in necrotic chromatin disposal. Int. J. Biochem. Cell Biol., 38, 297-306

Napirei M., Basnakian A. G., Apostolov E. O., Mannherz H. G. (2006) Deoxyribonuclease 1 aggravates acetaminophen-induced liver necrosis in male CD-1 mice. Hepatology, 43, 297-305

Napirei M., Wulf S., Eulitz D., Mannherz H. G., Klöckl T. (2005) Comparative characterization of rat deoxyribonuclease 1 (Dnase1) and murine deoxyribonuclease 1-like 3 (Dnase1l3). Biochem. J., 389, 355-364

Napirei M., Wulf S., Mannherz H. G. (2004) Chromatin breakdown during necrosis by serum Dnase1 and the plasminogen system. Arthritis Rheum., 50, 1873-1883

Napirei M., Ricken A., Eulitz D., Knoop H., Mannherz H. G. (2004) Expression pattern of the Deoxyribonuclease 1 gene: lessons from the Dnase1 knockout mouse. Biochem J., 380, 929-937

Jacob M., Napirei M., Ricken A., Dixkens C., Mannherz H. G. (2002) Histopathology of lupus-like nephritis in Dnase1-deficient mice in comparison to NZB/W F1 mice. Lupus, 11, 514-527

Napirei M., Karsunky H., Zevnik B., Stephan H., Mannherz H. G., Möröy, T. (2000) Features of systemic lupus erythematosus in Dnase1-deficient mice. Nat. Genet., 25, 177-181

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