Decreased hematopoiesis in bone marrow of mice with congestive heart failure.

Patients with heart failure are predisposed to infections and anemia, possibly due to reduced hematopoiesis. The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) is increased in heart failure, and it inhibits normal hematopoiesis, partly due to apoptosis through the effector molecule Fas. We examined bone marrow progenitor cells of mice with heart failure induced by acute myocardial infarction. The fraction of progenitor cells in mice with heart failure was only approximately 40% of control. Measured with in vitro clonal assays, the proliferative capacity of the progenitor cells in mice with heart failure was reduced to approximately 50% of control. Flow cytometry with specific markers revealed a threefold increase in apoptosis among progenitor cells from mice with heart failure. In these mice, TNF-alpha/Fas expression was increased in bone marrow natural killer (NK) and T cells, and these lymphocytes showed increased cytolytic activity in vitro against progenitor cells. We conclude that the TNF-alpha/Fas pathway in lymphocytes is activated in the bone marrow during heart failure, which may play a pathogenic role in the observed decrease in hematopoiesis.

[1]  J. Stanghelle,et al.  Depressed immunity and impaired proliferation of hematopoietic progenitor cells in patients with complete spinal cord injury. , 2000, Blood.

[2]  P. Boekstegers,et al.  Involvement of CD95/Apo1/Fas in cell death after myocardial ischemia. , 2000, Circulation.

[3]  P. Robbins,et al.  Soluble tumor necrosis factor receptor abrogates myocardial inflammation but not hypertrophy in cytokine-induced cardiomyopathy. , 2000, Circulation.

[4]  H. Drexler,et al.  The cardiac Fas (APO-1/CD95) Receptor/Fas ligand system : relation to diastolic wall stress in volume-overload hypertrophy in vivo and activation of the transcription factor AP-1 in cardiac myocytes. , 2000, Circulation.

[5]  A. Dart,et al.  Serial echocardiographic assessment of left ventricular dimensions and function after myocardial infarction in mice. , 2000, Cardiovascular research.

[6]  J. Böhm.  Gelatinous transformation of the bone marrow: the spectrum of underlying diseases. , 2000, The American journal of surgical pathology.

[7]  O. Sejersted,et al.  Pulmonary and cardiac expression of preproendothelin-1 mRNA are increased in heart failure after myocardial infarction in rats. Localization of preproendothelin-1 mRNA and endothelin peptide. , 1998, Cardiovascular research.

[8]  A. Matsumori,et al.  Cytokine gene expression after myocardial infarction in rat hearts: possible implication in left ventricular remodeling. , 1998, Circulation.

[9]  J. Price,et al.  Fas ligand is present in human erythroid colony-forming cells and interacts with Fas induced by interferon gamma to produce erythroid cell apoptosis. , 1998, Blood.

[10]  P. Iversen,et al.  No neuronal regulation of murine bone marrow function. , 1998, Blood.

[11]  C. Long,et al.  Cytokine expression increases in nonmyocytes from rats with postinfarction heart failure. , 1998, The American journal of physiology.

[12]  J. J. Smith,et al.  Ventricular remodeling in a mouse model of myocardial infarction. , 1998, The American journal of physiology.

[13]  Jaleel A. Miyan,et al.  Bone marrow innervation regulates cellular retention in the murine haemopoietic system , 1997, British journal of haematology.

[14]  K. Pulkki,et al.  Cytokines and cardiomyocyte death. , 1997, Annals of medicine.

[15]  H. Oral,et al.  Hemodynamic regulation of tumor necrosis factor-alpha gene and protein expression in adult feline myocardium. , 1997, Circulation research.

[16]  M. F. Shannon,et al.  Deoxyribonucleic acid triplex formation inhibits granulocyte macrophage colony-stimulating factor gene expression and suppresses growth in juvenile myelomonocytic leukemic cells. , 1997, The Journal of clinical investigation.

[17]  B. Nelson,et al.  The Apoptosis-inducing Granulocyte-Macrophage Colony-stimulating Factor (GM-CSF) Analog E21R Functions through Specific Regions of the Heterodimeric GM-CSF Receptor and Requires Interleukin-1β-converting Enzyme-like Proteases* , 1997, The Journal of Biological Chemistry.

[18]  G. Dorn,et al.  Sphingosine Mediates the Immediate Negative Inotropic Effects of Tumor Necrosis Factor-α in the Adult Mammalian Cardiac Myocyte* , 1997, The Journal of Biological Chemistry.

[19]  L. Sachs,et al.  The control of hematopoiesis and leukemia: from basic biology to the clinic. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[20]  J. McMurray,et al.  Heart failure – implications of the true size of the problem , 1996, Journal of internal medicine.

[21]  D. Mann,et al.  Tumor Necrosis Factor-α and Tumor Necrosis Factor Receptors in the Failing Human Heart , 1996 .

[22]  K. Takenaka,et al.  Functional expression of Fas antigen (CD95) on hematopoietic progenitor cells. , 1995, Blood.

[23]  N. Young,et al.  Fas antigen expression on CD34+ human marrow cells is induced by interferon gamma and tumor necrosis factor alpha and potentiates cytokine-mediated hematopoietic suppression in vitro. , 1995, Blood.

[24]  G. Lindeman,et al.  Analysis of hematopoiesis in max 41 transgenic mice that exhibit sustained elevations of blood granulocytes and monocytes. , 1995, Blood.

[25]  N. Nicola,et al.  The clonal proliferation of normal mouse hematopoietic cells: enhancement and suppression by colony-stimulating factor combinations. , 1992, Blood.

[26]  I Nicoletti,et al.  A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. , 1991, Journal of immunological methods.

[27]  H. Fillit,et al.  Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. , 1990, The New England journal of medicine.

[28]  G. Schreiner,et al.  Interleukin 1 and tumor necrosis factor inhibit cardiac myocyte beta-adrenergic responsiveness. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[29]  C. Herzog,et al.  [Interleukin 1 and tumor necrosis factor]. , 1987, Zeitschrift fur Rheumatologie.

[30]  G. Nicolaysen,et al.  Differences and similarities between human and rabbit neutrophil granulocyte responses in vitro: the effects of zymosan‐activated plasma, phorbol myristate acetate and n‐formyl‐methionyl‐leucyl‐phenylalanine , 1987, Acta anaesthesiologica Scandinavica.

[31]  A. Linker,et al.  Gelatinous transformation of the bone marrow. , 1978, Human pathology.