Ability Of Spleen Research Articles

Analysis of the Mutagenic and Apoptotic Effects of Tritiated Water on Spleen T Lymphocytes of Wild Mice and p53-Deficient Mice

A large amount of tritium is required as the fuel source for the nuclear fusion reaction. As a result, during the routine operation or in case of accidents, one of the major issues is the assessment of the biological effects of tritium released from nuclear fusion power plants. In this study, the mutagenic effects of tritiated water (HTO) were compared to those of 137Cs γ irradiation on spleen T lymphocytes of wild (p53+/+) mice and p53-deficient (p53-/-) mice. In both mice, TCR variant fractions induced by HTO was higher than those by simulation-irradiation of 137Cs γ rays. When compared on the basis of the induced TCR variant fractions in p53-/- mice at 3 Gy, tritium β rays appear to be 1.7 times more mutagenic than γ rays. On the other hand, in p53+/+ mice, HTO injection increased induced TCR variant fractions significantly, whereas simulation-irradiation did not increase those at all. In order to elucidate the reason responsible for this difference in p53+/+ mice, we investigated the apoptotic ability of spleen T lymphocytes. As a result, the apoptotic ability of spleen T lymphocytes from p53+/+ mice exposed to HTO was reduced significantly compared to that from p53+/+ mice not exposed.

Ability of spleen, peritoneal cavity, and lymph node B cells to reconstitute serum immunoglobulin in SCID mice.

The impact of intrinsic B lymphocyte heterogeneity and of microenvironmental influences on serum immunoglobulin production by B cells was examined by intravenous (i.v.) and intraperitoneal (i.p.) transfer of BALB/c and BALB.xid (X-chromosome-linked immunedefective; XID) lymph node (LN), splenic (SP) and peritoneal cavity (PerC) cells into severe-combined immune-defective (SCID) mice. The results indicate that each B-cell source restores all immunoglobulin classes within 5 weeks of transfer, the rates for each isotype, however, differ between the B-cell sources. Serum IgM levels were restored most rapidly by PerC cell transfer, followed by SP and LN cell transfer. In addition, normal immunoglobulin levels were reached in the absence of complete lymphoid reconstitution. Serum immunoglobulin phenotypes characteristic of the donor strain, e.g. reduced IgM and IgG3 production by XID B cells, were maintained after transfer into the SCID recipient. Microenvironmental influences were indicated by reduced immunoglobulin production after i.p. transfer and after i.v. transfer into irradiated SCID recipients. The data show that both B-cell type and microenvironment play significant roles in generating the heterogeneous pool of B cells required for humoral immunity.

Neuroregulation of natural suppressor cell activity.

The neuronal control of murine natural suppressor (NS) cell activity was studied in mice following lesion of the arcuate nucleus of the hypothalamus performed by the postnatal treatment with monosodium glutamate (MSG). The suppressor activity was evaluated as the ability of spleen or bone marrow cells (suppressors) to suppress the mitogen-induced lymphocytes proliferation of allogeneic Balb/c spleen cells (indicators). The study was carried out on three different inbred strains of mice (C57BL/6, DBA/2 and CBA). The results demonstrated that, in all strains used, the treatment of mice (12 day-old) with MSG led to a marked reduction of natural suppressor cell activity. This reduction was observed in both spleen and bone marrow, the lymphoid organs in which the NS cell activity is usually present. A reduced NS activity was also present in the bone marrow of MSG-treated adult mice, suggesting a permanent alteration of NS cell activity. These results provide additional support on neuromodulation of immune system.

Splenic macrophage activation and functions in amyloid enhancing factor-induced secondary amyloidosis Study of phagocytosis, killing, respiratory burst, and MHC class II surface expression

Secondary amyloidosis is a systemic disease characterized by the extracellular tissue deposition of insoluble fibrillar amyloid A protein. Aberrant metabolism of serum amyloid A protein by reticuloendothelial cells is thought to result in the accumulation of fibrils within the tissue. Treatment of mice with amyloid-enhancing factor (AEF) in conjunction with an inflammatory stimulus (i.e., AgNO3) induced amyloid deposition within 48-72 h. The activation state of a macrophage largely defines its enzymatic capabilities. In the studies reported here, we examined the effect of AEF on spleen macrophage activation using both functional and phenotypic assays. We found that while AEF in the presence or absence of AgNO3 has no apparent effect on the ability of spleen and liver macrophages to phagocytose or kill Listeria monocytogenes, it appears to block enhanced respiratory burst function (as measured by O2- production) observed with AgNO3 alone. AEF therefore seems capable of inhibiting certain macrophage activation-associated functions while not affecting others. Our activation phenotype studies, using surface Ia expression, reveal that AEF blocks the increase in number of splenic macrophages expressing Ia seen with AgNO3 alone. Treatment with interferon-gamma was found to restore decreased Ia expression in animals given AEF+AgNO3 but did not prevent amyloid A fibril deposition.

EL-4 metastases in spleen and bone marrow suppress the NK activity generated in these organs.

The relationship between metastatic cells in the spleen and bone marrow of tumor-bearing mice and the NK activity generated in vitro by cells obtained from these organs was investigated. EL-4 lymphoma and B16 melanoma cells injected intraperitoneally into syngeneic mice (10(6) cells/animal) killed the recipients in 16 days. These tumors had a different metastatic profile: EL-4 metastasized to the spleen and bone marrow while B16 did not. The number of metastatic cells was evaluated by plating spleen or bone-marrow cells of tumor-bearing mice in agarose cultures; in parallel, the ability of spleen and bone-marrow cells to generate NK activity in vitro was assessed. The presence of 10(5) EL-4 cells/10(6) spleen or bone-marrow cells correlated with a total lack of NK activity in these organs; in contrast, no decrease in NK activity was evident in the spleen or bone marrow of B16-bearing mice. The removal of metastatic EL-4 cells (by antibody and complement) from the spleen or bone marrow did not rescue the NK activity. The lack of NK activity in spleen and bone marrow colonized by metastatic cells was not due to induction of a suppressor cell in the host. Metastatic EL-4 cells appeared to have a direct and irreversible suppressive effect on the generation of NK activity by spleen or bone marrow. A possible cause-effect relationship between metastatic colonization of lymphoid organs and suppression of local NK activity is considered.

Inflammation and host resistance against pathogens.

After a review of all factors released in an inflammatory focus which act on pathogens, a summary of recent findings concerning the influence of an inflammation on the remote control of mouse resistance against pathogens is given. In treated mice, the ability of spleen and liver macrophages to killListeria was found to be increased between 3 and 18 days following the induction of the inflammation. An increased resistance against the Lewis carcinoma was found, even when the mice were treated one day after the inoculation of malignant cells. In the treated mice, an increased cellular multiplication was observed in bone marrow, thymus, spleen, lymph nodes whereas no variations were observed in other tissues. The higher host resistance is correlated with an increased leucopoiesis and the activation of liver and spleen macrophages. The serum of treated animals is ablein vitro to activate peritoneal macrophages against Lewis carcinoma cells, to stimulate the multiplication of bone marrow cells and to agglutinate malignant cells. In order to explain the mechanisms of such an increased host resistance, investigations were undertaken to isolate and characterize possible active substances in the granuloma and in the serum from granuloma-bearing mice, and to check the possible activity of mediators of inflammatory reactions. Concerning the granuloma and the serum, it was possible, following electrofocusing, to extract and to isolate a fraction which is able to protect mice against a lethal inoculum ofListeria. Among the known mediators of acute inflammation, it was found not only that kinins are able to increase the spreading of macrophagesin vitro but that kinins or some of their degradation products are able,in vivo, to increase the resistance of mice againstListeria and the Lewis carcinoma. These results emphasize the importance of local non-specific inflammatory reactions on macrophages.

Responses of lymphocytes of hydrocortisone-stimulated and adrenalectomized mice to h alloantigens

The ability of spleen, bone marrow, and thymus cells of intact and adrenalectomized CBA mice, and of CBA mice receiving single or repeated doses of hydrocortisone, to induce a lymph node “graft versus host” reaction (GVHR) in (CBA×C57BL)F1 hybrids was determined. The ability of the spleen and bone marrow cells to induce GVHR was increased two days after administration of 2.5 mg hydrocortisone, whereas the ability of the thymus cells was unchanged. Seven days and, in particular, 15 days after injection of hydrocortisone, the spleen cells were less active. Activity of the thymocytes in GVHR was increased two days after repeated daily injections of the hormone in a dose of 0.25 mg for 18 days, whereas activity of the spleen and bone marrow cells was unchanged.

The effects of intravenous administration of Methanol Extraction Residue (MER) of tubercle bacilli in the dog

The effects of intravenous administration of the insoluble methanol extraction residue (MER) of tubercle bacilli were studied in six adult Beagle dogs. All animals were closely monitored for clinical signs, alterations in serum biochemistry or hematologic values, and for gross and histologic findings at autopsy. Immune responsiveness was assessed by skin reactivity to test antigens and by ability of spleen and lymph node lymphocytes to produce macrophage activating factor (MAF).

Changes in H-alloantigen-recognition function of lymphocytes after hydrocortisone administration in mice

The ability of spleen, thymus, and bone-marrow cells of intact (control) and hydrocortisone-treated (experiment) CBA mice to induce a lymph node graft versus host reaction (GVHR) in (CBA×C57BL)F1 hybrids was compared. After injection of hydrocortisone into the donors in a dose of 2.5 mg per mouse their spleen cells induced a more active GVHR, as shown by an increase in the lymph node indices and in the percentage of immunoblasts in the regional (popliteal) lymh node compared with the control. After transfer of thymus cells of hydrocortisone-treated donors the number of immunoblasts was higher than, but the weight of the lymph node was almost the same as in the control. Conversely, after injection of bone marrow cells from hydrocortisone-treated donors, the lymph node enlarged whereas the percentage of immunoblasts did not increase above the control. Consequently, when the increase in the hydrocortisone level is exogenous in nature, the cell populations of the spleen and thymus contain a higher proportion of T lymphocytes, which respond by proliferation to contact with H alloantigens.

The Long-Term Effects of X-Irradiation on the Ability of the Spleen to Support Clonogenic Proliferation

A modified spleen colony method was used to measure the functional ability of the irradiated spleen to support clonogenic proliferation. This was assayed by counting the number of exogenous colonies formed by normal bone marrow cells injected into recipient mice whose spleens had previously been irradiated. A shallow dose-related decrease in the ability of irradiated mouse spleen to support clonal growth was seen at all times after splenic irradiation. These dose-response relationships do not resemble the usual clonogenic survival curves. The reduction in colony number produced by normal bone marrow cells did not decrease below 0.4 even when the recipient spleen had received as much as 3000 rads. Recuperation of the ability of irradiated mouse spleen to support clonal growth was observed at intervals of 6 and 9 mo. This appeared to be a temporary recuperation, since a second reduction was seen at 12 mo. An absence of repair was demonstrated when 2000 rads was fractionated into two doses delivered 6 hr to ...