strontium-radioisotopes and Leukopenia

The present paper focuses on the analysis of data resulting from 50-y studies involving assessment of the hemopoiesis state in Techa riverside residents chronically exposed to radiation and evaluation of the bone tissue status for people with Sr incorporation at late time after the intakes.. 1. In the late period after the start of chronic radiation exposure (50 y later) only a few individuals with red bone marrow doses reaching about 1.8 Gy (mean dose of 0.66 Gy) had a marked peripheral blood leucopenia, and the incidence of neutropenia, lymphopenia and thrombocypenia in the exposed group did not exceed that noted in the control group. The results of our observations indicate the spontaneous recovery of the hemopoietic system of residents of the Techa riverside villages. Thus, the adaptation mechanisms of hemopoiesis to the long-term chronic exposure in the range of low to intermediate doses are sufficiently effective; 2. About half of the people with Sr incorporation and the control group have changes in bone tissue expressed by different stages of osteoporosis. Age is a determinative factor of bone tissue involution in women while some tendency of Sr influence on the intensity of osteoporosis is revealed in the male group.

Topics: Aged; Aged, 80 and over; Bone and Bones; Bone Marrow; Case-Control Studies; Environmental Exposure; Female; Hematopoiesis; Humans; Leukopenia; Male; Middle Aged; Osteoporosis; Russia; Strontium Radioisotopes; Water Pollutants, Radioactive

Topics: Animals; Antibodies, Monoclonal; Cell Count; Colony-Forming Units Assay; Dendritic Cells; Epidermis; Female; In Vitro Techniques; Leukopenia; Lymph Nodes; Mice; Mice, Inbred BALB C; Monocytes; Splenectomy; Strontium Radioisotopes; T-Lymphocytes; Thymus Gland

Topics: Animals; Bone Marrow; Cell Cycle; Female; Leukopenia; Macrophages; Mice; Mice, Inbred C3H; Monocytes; Pulmonary Alveoli; Radiation Injuries, Experimental; Spleen; Strontium Radioisotopes

The cytokinetic behavior of pulmonary alveolar macrophages (PAM) was studied by pulse labeling with 3HTdB in mice made monocytopenic by a single intravenous injection of the bone-seeking isotope strontium-89 (89Sr). In the presence or absence of blood monocytes, PAM population size was unchanged for up to 1 month of chronic, severe monocytopenia. Pulse-labeling studies performed during monocytopenia show that in control mice PAM population half-times were 17.8 days with a potential doubling time of 39 days, whereas T1/2 was 14.8 days with a 28.5 day population doubling time for PAM in 89Sr-treated mice. Analysis of the halving times of the PAM mean grain count and the halving times of the most highly pulse-labeled cohorts suggested that PAM cell cycle times (Tc) were 5.1 days with a PAM rate of disappearance of 10.8%/day in 88Sr-treated mice and Tc of 6.6 days with a PAM rate of disappearance of 11.4%/day in 89Sr-treated mice. As measured by 3HTdR-labeling techniques, these cytokinetic values are in close approximation to each other, suggesting that 89Sr treatment did not significantly alter either PAM population size or cytokinetic behavior. Employing experimental values it was possible to construct a simple model of PAM population growth that supports the concept that the PAM population is self-renewing in the adult mouse. Taken together, the data show that a major portion of the resident PAM need not depend on the daily influx of peripheral blood monocytes to maintain themselves in a kinetically steady state.

Topics: Animals; Cell Cycle; DNA Replication; Female; Kinetics; Leukopenia; Macrophages; Mice; Mice, Inbred ICR; Monocytes; Strontium Radioisotopes; Thymidine; Tritium

The i.p. injection of Corynebacterium parvum (CP) into CBA/J mice effected increases in macrophage colony-forming cells (M-CFC) when spleen cells were cultured with L cell culture filtrate as a source of colony-stimulating factor. Significant increases in phagocytic macrophages (M phi) with Fc receptors for IgG2a and IgG2b immune complexes were additionally noted among the spleen cells in these mice. These M phi effectively inhibited Con A-induced lymphocyte proliferation, probably reflecting a 10-fold increase above normal controls in prostaglandin E to 47 ng/3 X 10(6) spleen cells/ml. To determine whether the suppressor M phi are immediate derivatives of splenic M-CFC, we tried to induce suppressor M phi by the injection of CP into mice depleted of bone marrow M-CFC by the earlier administration of the bone-seeking isotope, 89Sr. This procedure reduced M-CFC in the bone marrow to less than 1% of normal for more than 30 days. Monocytes in the blood fell to 5% of normal by day 10 and were 30% on day 30. Levels of resident peritoneal M phi showed relatively little change in this period. By contrast, splenic M-CFC increased to 20-fold higher than the "cold" 88Sr controls. CP-induced suppressor M phi activity, however, was sharply reduced in 89Sr marrow-depleted mice on day 10, despite the striking increase in M-CFC. There was a threefold increase in the number of phagocytic M phi binding IgG2a immune complexes, with no significant increase in IgG2b binding M phi. The kinetics of recovery of suppressor M phi activity showed that on days 20, 30, and 50 after 89Sr injection the activities reached 20%, 30%, and 70% of the "cold" control, respectively, and correlated with the recovery of significant levels of M-CFC in the bone marrow. Taken together, these observations suggest that splenic M-CFC are not an immediate source of PGE-suppressor M phi in vivo. It appears more likely that the CP-inducible suppressor M phi, in particular, originate from radiosensitive bone marrow cells or require for differentiation a microenvironment provided by bone marrow cells. The data also suggest that the expression of the Fc gamma 2b receptor and of suppressor activity by CP-induced splenic M phi are related phenomena.

Topics: Animals; Bone Marrow; Colony-Forming Units Assay; Female; Immunosuppression Therapy; Leukopenia; Macrophage Activation; Macrophages; Mice; Mice, Inbred CBA; Propionibacterium acnes; Prostaglandins E; Receptors, Fc; Receptors, IgG; Spleen; Strontium Radioisotopes

Mechanisms underlying mononuclear phagocyte specialization are being probed by studying suppressor macrophages (M phi) as a reference population in mouse models with impaired blood monocyte formation. Splenic suppressor M phi, defined by PGE-mediated inhibition of Con A-induced T lymphocyte proliferation are induced by the i.p. administration of Corynebacterium parvum (CP). Mice severely depleted of bone marrow and blood monocytes by treatment with 89Sr fail to show this suppressor M phi response to CP, although M phi-forming stem cells, assessed as splenic M-CFC in vitro, are increased 20-fold. These observations suggest that radiosensitive bone marrow stem cells are necessary for the generation of both suppressor M phi and monocytes and that one such stem cell may be common to both types of mononuclear phagocytes. This notion was explored further by employing congenitally anemic mice of the genotype S1/S1d in which the hemopoietic microenvironment is genetically defective and thus unable to support the proliferation, differentiation, and function of stem cells. The congenital defect was found to be additionally expressed in the S1/S1d mouse by a monocytopenia of less than 10% of the values in normal congenic littermate controls and by the failure of splenic M-CFC to increase in response to CP. PGE-producing suppressor M phi expressing Fc gamma 2b receptors, however, were induced by CP in S1/S1d mice with no significant diminution of suppressor activity. These data establish the fact that significant impairment of the formation of monocytes is part of the overall hemopoietic defect in S1/S1d mice. PGE-producing suppressor M phi, however, were inducible at normal functional levels in the presence of a profound monocytopenia, and therefore appear to be independent of the mechanisms that regulate blood monocyte formation. Ablation of the bone marrow with 89Sr resulted in failure of CP to induce suppressor M phi in the spleens of the S1/S1d mice as in the littermate controls. Other observations in the present study, when taken with data from the 89Sr model, show the additional independence of these suppressor M phi from splenic M-CFC. In aggregate, these findings delineate three functionally definable populations of mononuclear phagocytes that appear to be independently regulated.

Topics: Anemia, Hemolytic, Congenital; Animals; Bone Marrow; Colony-Forming Units Assay; Genotype; Hematopoietic Stem Cells; Immunosuppression Therapy; Leukopenia; Macrophage Activation; Macrophages; Male; Mice; Mice, Mutant Strains; Peritoneal Cavity; Propionibacterium acnes; Prostaglandins E; Spleen; Strontium Radioisotopes