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.
Iversen
Per Ole
PO
Institute for Nutrition Research, University of Oslo, Oslo, Norway. poiversen@hotmail.com
Woldbaek
Per Reidar
PR
Tønnessen
Theis
T
Christensen
Geir
G
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001853:Bone Marrow / Q000473:pathology* / Q000503:physiopathology; D002455:Cell Division / Q000276:immunology; D053222:Fas Ligand Protein; D015870:Gene Expression / Q000276:immunology; D006333:Heart Failure / Q000276:immunology* / Q000473:pathology; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000473:pathology; D007962:Leukocytes / Q000166:cytology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009203:Myocardial Infarction / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha