Reduced thymocyte proliferation but not increased apoptosis as a possible cause of thymus atrophy in iron-deficient mice.
Iron deficiency induces thymus atrophy in laboratory animals and very likely in humans by unknown mechanisms. The atrophy is associated with impaired cell-mediated immunity. In this study, we tested the hypothesis that thymus atrophy is a result of increased apoptosis and reduced thymocyte proliferation. Thymocytes were obtained from twenty-seven control, twenty-seven pairfed, twenty-seven iron-deficient (ID) mice; twelve and fourteen ID mice that received the control diet (0.9 mmol/kg versus 0.09 mmol/kg for the ID diet) for 1 d (repletion, R1) and 3 d (R3), respectively. Cell cycle analysis and apoptosis were studied by flow cytometry using propidium iodide staining and terminal deoxyuridine nick end labeling of DNA breaks assay respectively. When mice were killed, haemoglobin, haematocrit, and liver iron stores of ID, R1, and R3 mice were 25-40 % of those of control and pairfed mice Absolute and relative thymus weights and thymocyte numbers were 19 to 68 % lower in ID, R1, and R3 than in control and pairfed groups We found no significant difference among groups in the percentage of cells undergoing apoptosis. A higher percentage of thymocytes from ID and R1 mice than those of control, pairfed, and R3 mice were in the resting phase of the normal cell cycle Conversely, a lower percentage of thymocytes from ID and R1 mice than those from control, pairfed, and R3 mice were in the DNA synthesis phase and late phase of DNA synthesis and onset of mitosis (G2-M) Indicators of iron status positively correlated (r 0.3 to 0.56) with the percentage of thymocytes in the G2-M phase Results suggest that reduced cell proliferation but not increased apoptosis is the cause of thymus atrophy associated with iron deficiency.
Kuvibidila
S R
SR
Department of Pediatrics, Louisiana State University Health Sciences Center, 1542 Tulane Avenue, New Orleans LA 70112, USA. skuvib@lsuhsc.edu
Porretta
C
C
Surendra Baliga
B
B
Leiva
L E
LE
D018798:Anemia, Iron-Deficiency / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D017209:Apoptosis; D001284:Atrophy / Q000209:etiology; D002452:Cell Count; D002453:Cell Cycle; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006400:Hematocrit; D006454:Hemoglobins / Q000032:analysis; D020287:In Situ Nick-End Labeling; D007501:Iron / Q000032:analysis; D008099:Liver / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D013950:Thymus Gland / Q000473:pathology*
D006454:Hemoglobins; D007501:Iron