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PubMed1976

Histological alterations in spleen and bone marrow colonies produced by irradiation of the donor mice.

The previously reported decrease in the ratio of erythrocytic (E): granulocytic (G) spleen colonies observed 8 days after bone marrow transplantation, when the donors had been x-irradiated up to 4 hours before the marrow was taken for transfer, was confirmed. The effect of taking the marrow between 4 hours and 13 days after x-irradiation, on the E:G ratio in both spleen and femoral bone marrow colonies, has been studied in detail. The reversion to a normal E:G ratio in spleen colonies assessed at 8 or 10 days was associated with increases in this ratio of colonies in the femoral bone marrow. Transplantation of cell suspensions prepared from the spleen and femoral bone marrow of primary recipients 8 days after the initial transfer produced a histological distribution of 8-day colonies in secondary recipients which was indpendent of x-irradiation of the donor. The data suggest that a hypothesis involving CFU migration within the spleen and, possibly, from the bone marrow to the spleen, provides a more satisfactory explanation of the data than one involving two CFU populations with different radiosensitivities.

Animals↗
PubMed1994

Constitutive and inducible Rel/NF-kappa B activities in mouse thymus and spleen.

We have studied the expression of members of the rel family of transcription factors and ikba in mouse thymus and spleen by in situ hybridization. Our results show that the rel genes have different temporal and spatial patterns of expression suggesting distinct roles in these lymphoid tissues. The Rel/NF-kappa B proteins and I kappa B alpha in thymus and spleen were also analysed by Western blotting and electrophoretic mobility shift assays. Although RelB protein is present at significantly lower levels in thymus and spleen extracts when compared to RelA, in both tissues the predominant kappa B-binding activity consists of p50/RelB and p52/RelB heterodimers and only very little binding of RelA-containing complexes to kappa B sites was detected. Significant binding of c-Rel complexes was only found in spleen extracts. Treatment of thymus and spleen extracts with deoxycholate (DOC), however, results in a strong increase in binding to kappa B sites of both RelA and c-Rel complexes. In contrast, binding of RelB complexes is not induced after DOC treatment. Our results suggest a differential role of Rel/NF-kappa B complexes in mouse thymus and spleen with RelB heterodimers representing the constitutive kappa B-binding activity, whereas RelA and c-Rel complexes most likely are involved in inducible kappa B-binding and gene activation.

Animals↗
PubMed1994

Cellular basis of differential responsiveness of lymph nodes and spleen to 23-valent Pnu-Imune vaccine.

Subcutaneous administration with 23-valent pneumococcal polysaccharide vaccine (Pnu-Imune) elicited a good antipneumococcal capsular polysaccharide response from the spleen but not from peripheral lymph nodes (LN) (cervical, brachial, axillary, popliteal, inguinal) of BALB/c mice. To evaluate the cellular basis of the unresponsiveness of LN to this vaccine and to identify the cell types in spleen that are necessary for induction of polysaccharide Ab responses, a reliable in vitro culture system was developed to obtain plaque-forming cell responses to the Pnu-Imune vaccine. The in vitro antipneumococcal polysaccharide response of mouse spleen cells was found to be relatively T cell independent. Unlike spleen cells, LN cells did not respond to the Pnu-Imune vaccine in vitro. However, LN cells responded to Pnu-Imune vaccine when co-cultured with irradiated spleen cells or splenic dendritic cells but not with accessory cell-depleted spleen cells. LN cells were found to contain the necessary accessory cells that can support the polysaccharide response but in reduced numbers. The LN response to the vaccine was also reconstituted by IL-1 or Th2-associated cytokine IL-5. In contrast, IFN-gamma, a Th1 cell-derived lymphokine was able to suppress the in vitro splenic response to the vaccine suggesting that differential activation of Th1 and Th2 types of Th cells might be one mechanism by which T cells regulate Ab responses to pneumococcal polysaccharides.

Animals↗
PubMed1976

In vitro induction of cytotoxicity against syngeneic mastocytoma and its suppression by spleen and thymus cells from tumor-bearing mice.

P815 times 2 mastocytoma cells, when injected subcutaneously into syngeneic DBA/2 mice, induced T lymphocytemediated cytotoxicity in the mice. During the course of tumor growth this cytotoxic activity decreased and ultimately the tumor killed the mice. When spleen cells from mice with tumors in the early stages of growth were incubated in vitro with mitomycin C-treated tumor cells, specific cytotoxicity mediated by T lymphocytes was developed. In contrast, spleen cells, taken from mice with tumors at a later stage in their growth, did not develop cytotoxic activity. The unresponsiveness of spleen cells from mice with tumors in the latter stages of growth seemed to be due to the presence of suppressor cells since in vitro development of cytotoxicity by spleen cells from early tumor-bearing mice were inhibited by the addition of spleen cells or thymocytes from mice with progressively growing tumors. Normal spleen cells or thymocytes did not affect the response.

Animals↗
PubMed1993

[Quantitative and qualitative observations of spleens removed from patients].

UNLABELLED: The spleens of 100 patients (ITP 60 cases, hypersplenism 20 cases, traumatic rupture of spleen 20 cases) were examined histologically and by electron microscopy. Measurements of the spleens removed from ITP patients were taken and compared to those of the other two groups. Short and long term post operative results were compared. RESULTS: 1. Spleens from the ITP group had characteristics different from those from the hypersplenism (hepatocirrhosis) and control groups; 2. the ITP patients whose spleen is twice the weight of average had better long term response to splenectomy; 3. the mean diameter of splenic follicles greater than 500 microns and the average diameter of germinal centers greater than 200 microns were the criteria for long term response to splenectomy. Therefore, histological examination of excised ITP spleen can predict the possible long term effect of splenectomy.

Adolescent↗
PubMed1993

Specific binding of [125I]iodomelatonin in pigeon and quail spleen membrane preparations and effect with hydrocortisone-treatment.

[125I]Iodomelatonin binding sites were studied in the spleens of pigeon and quail. Scatchard analyses of the membrane preparations collected at midday (12:00) revealed an equilibrium dissociation constant (Kd) of 250 +/- 74 pmol.L-1 and a maximal number of binding sites (Bmax) of 13.4 +/- 1.8 fmol/mg protein in the pigeon spleen and Kd = 390 +/- 132 pmol.L-1, Bmax = 21.3 +/- 3.7 fmol/mg protein in the quail spleen. Circadian studies indicated that spleens collected at midnight (24:00) had 53% and 70.9% less [125I]iodomelatonin binding sites than the samples collected at midday in the pigeon and quail, respectively. Specificity studies showed only melatonin and 6-chloromelatonin had significant inhibition to [125I]iodomelatonin binding. Hydrocortisone 15 mg.kg-1 x d-1 im for 5 d selectively increased [125I] iodomelatonin binding sites in pigeon spleen. These results suggest that spleen is a site of melatonin action outside the brain.

Animals↗
PubMedDate not supplied

Multiple effects caused by anti-IL-4 mAb inoculation in the thymus and spleen of adult mice.

We investigated the physiological role of IL-4 in the thymus and spleen by administering a neutralizing monoclonal anti-IL-4 antibody (11B11 mAb) into adult mice for 7 or 14 days. After this treatment the thymus decreased in size, this was mainly attributed to a decrease in the CD4+CD8+ subset after 7 days and both the CD4+CD8+ and the CD4+CD8- subsets after 14 days. These data suggest that IL-4 has a role in CD4+CD8+ thymocyte development and can differentially modulate the maturation of CD4+CD8- thymocytes in adult mice. Conversely, anti-IL-4 inoculation induced an increase in spleen size. After 7 days of treatment this enlargement appeared to be due to a increase in number of immature cells, the majority of which were CD4-CD8-alpha beta TCR-B220-slg-Ia-Mac-1-Pgp1 positive. After 14 days, an expanded spleen size was mainly due to inflated numbers of mature CD4+CD8-, B and Mac-1+ cells. In addition, we showed that anti-IL4 mAb in vivo enhanced the CD4-CD8-alpha beta TCRlow subset within the spleen after 7 days which is also observed at 14 days of treatment. Finally, we demonstrated that anti-IL-4 mAb treatment is highly stimulatory for hemopoietic activity in the adult spleen. Taken together, these results support the notion that IL-4 acts in vivo, directly or indirectly, on T cell differentiation in the thymus and T subsets homeostasis as well as on other cell types in the spleen of adult mice.

Animals↗
PubMed1993

Transactivation of interleukin-2 gene via the nuclear proteins from spleen and brain cells.

Immunomodulatory action of nuclear proteins derived from spleen and brain of immunized rats was found in ConA-stimulated mouse spleen lymphocyte cultures. In vitro experiments on 32P- or Dig-labeled promoter-enhancer region (-548 bp) of the human interleukin-2 (IL-2) gene showed specific DNA-nuclear protein complex formation for spleen (6-14 kD) and brain (21 kD) proteins. The functional influence of these trans-factors on the IL-2 promoter region was studied in the model system of Jurkat cells with the firefly luciferase (Luc) reporter gene. The spleen and brain proteins were shown to influence the membrane surface properties of thymic and spleen cells as revealed in a two-phase aqueous system. We conclude that both spleen and brain from immunized rats contain certain protein trans-factors which can be active in T cells and display a common mode of regulatory action the level of IL-2 gene.

Animals↗
PubMed1993

Verification of a varying threshold edge detection SPECT technique for spleen volume: a comparison with computed tomography volumes.

SPECT enables quantitation of organ volume with radionuclide techniques using threshold edge detection methods. Previous phantom studies showed that a negative correlation exists between volume and threshold value. In those studies, the use of calibration curves were believed to correct for volume dependence on threshold values. The aim of this study was to evaluate the accuracy of spleen volume determination in 20 patients with SPECT by employing a varying threshold edge detection technique with volumes derived from CT. All patients had both radionuclide and CT examinations that were reconstructed with a filtered backprojection algorithm. During SPECT reconstruction, transverse slices were obtained with attenuation correction (Method A) and without attenuation correction (Method B). CT volumes were calculated from manually drawn regions of interest, whereas SPECT volumes were calculated with an automated algorithm using previously determined calibration curves. A confidence interval for calculated SPECT volumes also was calculated because of possible errors in the threshold value. The spleen volumes studied ranged from 91.2 ml to 1660.1 ml. Regression analysis yielded equations of CT = 0.97 SPECT + 7.07 (r = 0.996) and CT = 1.05 SPECT - 19.25 (r = 0.990) between CT and SPECT spleen volumes with a standard error of the y estimates of 31.10 ml and 54.47 ml, respectively. A mean percentage difference of 10.5% +/- 7.6% and 11.4% +/- 6.6% in spleen volume was obtained for Methods A and B in comparison with CT spleen volumes. The threshold value varied between 40.9% and 32.4% for Method A and between 41.2% and 28.5% for Method B because the spleen volume is increased. The varying threshold edge detection technique described in this paper can be implemented successfully in the clinical setting.

Adult↗
PubMed1993

Ultrastructural characteristics of Fc epsilon R-positive basophils in the spleen and bone marrow of mice immunized with goat anti-mouse IgD antibody.

BACKGROUND: Previous work showed that injection of mice with goat anti-mouse IgD antibodies results in increased numbers of Fc epsilon R-positive, non-B, non-T cells in the spleen and Fc epsilon R-positive cells in the bone marrow, and that some of these cells had ultrastructural features of basophils. Fc epsilon R-positive, non-B, non-T cells express virtually all of the capacity of mouse splenic "non-B, non-T cells" to produce interleukin-4 in response to stimulation by cross-linking of Fc epsilon R or Fc gamma R, or by the calcium ionophore, ionomycin. EXPERIMENTAL DESIGN: The present study is a detailed ultrastructural analysis of Fc epsilon R-positive bone marrow cells or Fc epsilon R-positive splenic non-B, non-T cells sorted from mice injected with goat anti-mouse IgD antibody and of Fc epsilon R-positive bone marrow cells or spleen cells pooled from normal mice not injected with goat anti-IgD. RESULTS: Basophils represented the majority (90%) of the granulated cells present in the Fc epsilon R-positive splenic non-B, non-T cells or Fc epsilon R-positive bone marrow cells of goat anti-IgD-injected mice. In contrast, the cytoplasmic granule-containing Fc epsilon R-negative cells sorted from spleen or bone marrow of goat anti-IgD-injected animals contained predominantly a mixture of neutrophils, eosinophils, monocytes and their precursors. Both the Fc epsilon R-positive and -negative preparations contained rare (< 5%) cells with ultrastructural features of very immature mast cells. Basophils were also identified in Fc epsilon R-positive cells sorted from total bone marrow cells or spleen cells of normal mice not injected with goat anti-IgD. CONCLUSIONS: Taken together with data concerning the numbers of Fc epsilon R-positive, non-B, non-T cells in the spleen, and Fc epsilon R-positive B220-negative cells in the bone marrow, these ultrastructural findings indicate that injection of mice with goat anti-IgD results in increased numbers of basophils, particularly in the spleen, that exhibit an 8-fold increase in basophils as a result of injection of goat anti-IgD.

Animals↗
PubMedDate not supplied

Effect of IFN-gamma administration in virgin and pregnant mice: distribution of lymphoid and myeloid cells in the spleen.

Administration of Interferon-gamma (IFN gamma) is used in the therapeutic approach for mainly cancer treatment and viral infections in vivo. Recently we observed some important pathologic dysfunctions caused by IFN-gamma administration to pregnant mice. This treatment affected not only the growth and development of the feto-placental unit, but also, among other hematologic disorders, caused splenomegaly to the mother. In an effort to explain the observed hypersplenism, we have analysed the behaviour of macrophages, B and T lymphocytes in the spleen of virgin and pregnant mice after intraperitoneal administration of low IFN-gamma doses. Although the percentage of myeloid Mac-1 and F4/80 positive cells in spleen cell suspensions of virgin and pregnant mice do not change with the IFN-gamma treatment, immunoperoxidase staining of frozen spleen sections shows that in pregnant mice the monocytic cells accumulate at the central white pulp area of the organ, whereas in non-pregnant mice these cells are mainly found at the peripheral red pulp area. In contrast, the same treatment was shown to increase the numbers of Ly5 positive B cells in both virgin and pregnant mice, whereas B cells were found to form clusters only in the case of pregnant animals. We also show that IFN-gamma increases the numbers of Tcyt/sup (Ly2 positive cells) and TH (L3T4 positive cells) in the spleen of virgin mice but not in pregnant mice. Both populations display a physiologic distribution in the white pulp of the organ as assessed by immunoperoxidase staining of frozen spleen sections. Interestingly, the distribution pattern of IL-2- and IL-4-producing cells, which reflects the presence of Th1 and Th2 subpopulations was different in pregnant and virgin mice. Gestating females had IL-2 producing cells dispersed in the white pulp area, whereas IL-4 producing cells formed clusters mainly at the periphery of the organ. Virgin females had almost undetectable levels of IL-4 producing cells, whereas IL-2 producing cells were found at the periphery. Our results indicate that IFN-gamma alters the equilibrium between Th1 and Th2 cells, which in turn is responsible for the redistribution of myeloid and lymphoid cells in the spleen of pregnant mice thereby explaining the development of an active immune/inflammatory reaction.

Animals↗
PubMed1996

Effects of low dose gamma-ray irradiation on peripheral leukocyte counts and spleen of mice.

OBJECTIVE: To study the effects of low dose gamma-ray irradiation on peripheral leukocyte counts and spleen weight of mice. MATERIALS AND METHODS: Two hundred male mice of ICR strain were divided into four groups. Group A served as normal control. Groups B, C and D, the experimental groups were treated with 5, 50 and 100 cGy (exposure dose in air) of whole body gamma-ray irradiation respectively. The leukocyte counts and its differential counts, body weight and the spleen weight of mice were measured on days 1, 5, 12, 19, 26 and 33 after irradiation. The relative spleen weight derived from the data of body weight and spleen weight was also calculated in tested animals. RESULTS: The leukocytes and its differential counts and relative spleen weight in mice decreased after 100 cGy gamma-ray irradiation. Fifty cGy gamma-ray irradiation could inhibit the leukocyte and its differential counts. The lowest dose, 5 cGy had no considerable damage. CONCLUSIONS: One hundred cGy of 137Cs gamma-ray irradiation had an inhibitory effect on counts of total leukocyte, lymphocyte, neutrophil, monocyte, spleen weight and body weight, while 50 cGy gamma-ray irradiation had an evident inhibition on peripheral leukocytes and its differential counts in mice. However, 5 cGy gamma-ray irradiation had no obvious inhibition in the tested mice in the period of the investigation.

Animals↗
PubMed1997

The antigen-bearing eye and the spleen are indispensable in maintaining anterior chamber-associated immune deviation.

PURPOSE: To investigate the role of the eye and the spleen in maintaining suppression of delayed-type hypersensitivity (DTH) after anterior chamber (AC) inoculation of allogeneic splenocytes. METHODS: Suppression of DTH response was tested in BALB/c mice after AC inoculation of allogeneic B10.D2 splenocytes. Seven days after AC injection, the antigen-inoculated eyes were enucleated or the spleens were removed. After enculeation or splenectomy at different time intervals, DTH responses in groups of the BALB/c mice were examined. Spleen components obtained from BALB/c mice that had been primed by B10.D2 splenocytes in the AC 7 days earlier were transferred intravenously to groups of naive syngeneic acceptors. At various intervals after adoptive transfer, variations of DTH responses were tested. RESULTS: Inoculation of B10.D2 splenocytes to the AC of BALB/c mice induced antigen-specific suppression of DTH. Either enucleation of the antigen-inoculated eyes or splenectomy weakened the DTH-suppressive effect within 5 weeks and abolished it within 9 weeks, whereas the mice retaining both antigen-inoculated eyes and spleens maintained longstanding DTH suppression. Adoptive transfer of spleen components to syngeneic acceptors demonstrated DTH suppression for only 3 weeks. CONCLUSIONS: The antigen-inoculated eye and spleen are required for long-standing suppression of DTH after AC inoculation of allogeneic splenocytes.

Adoptive Transfer↗
PubMed1976

[Splenomegaly reaction of the chick embryo following chorio-allantoid graft of chicken-spleen fragments].

The spleen enhancement reaction of the chick embryo, following the insertion (grafting or injection procedure) of homologous spleen cells is one of the results of the graft-versus-host reaction (G.V.H. reaction). Irrespective of the usual kinds of G.V.H. reaction measured, it has been proved that the relation between the number of immuno competent cells and the reaction intensity is linear. Our study shows that the relation is not the same when the chorio-allantois membrane grafting procedure is used instead of injection into the veins. However, two facts remain unchanged 1) the minimal amount of spleen cells sufficient to provoke a spleen enhancement is low, 2) there is a link between the number of homologous spleen cells and the rate of spleen enhancement, but in this case it was not shown to be linear. In the light of this, the role played by the chorio-allantois membrane is being debated.

Allantois↗
PubMed1996

[Experimental study of immunity in anti-plasmodium infection on preserved spleen and splenectomized mice].

OBJECTIVE: To investigate the function of the spleen as well as the changes of splenic function after hemisplenectomy and hemisplenic autotransplanted in plasmodium yoelili infected mice (first and second infection). METHODS: 336 mice were divided into six groups: 1. total splenectomy, 2. hemisplenectomy, 3. hemisplenic autotransplanted, 4. sham-operation, 5. total splenectomy of 2nd infection, 6. sham-operation of the 2nd infection. 3 months after operation (1-4) or 15 day after 1st infection and operation (5-6) in mice intraperitoneal inoculations were initiated. RESULTS: 1. First infection: in total splenectomy group the antiplasmodium antibody reduced, the remanent rate of 51Cr-RBC in circulation was high, RBC count continously decreased, parasitized erytrocytes still were seen after 1 month. These changes were mild in the preserved spleen. But the production of antiplasmodium antibody and spleen uptake rate of 51Cr-RBC of the hemisplenic autotrans aplaned were rather lower than those of the shamoperate group. 2. Second lethal yoelli infection: in the mice of shamoperation of 2nd yoelii infection the parasitized erytrocyte was lower than that of shamoperated group, but the higher level antiplasmodium antibody and uptake rates of 51Cr-RBC of unit weight splenic tissue. CONCLUSIONS: Under the plasmodium infection preserved hemispleen alternate normal spleen to play the immunologic role, splenic tissue autotransplantation can fairly restore the partial function of spleen. Different preserved spleen method is a useful operation for clinic.

Animals↗
PubMed1976

Erythropoietic events in cultured embryonic mouse spleen.

The events of erythropoiesis in cultured embryonic mouse spleens isolated on the 12th day of gestation were compared with those occurring in spleens of corresponding gestational days in vivo. It was found that the development of erythroid precursors in the cultured spleen depended on the presence of erythropoietin in the culture medium. A progressive increase in the number of erythroid precursors, with a marked shift to mature cells, was observed in spleens cultured with erythropoietin. Although the origin of the hemocytoblasts in the spleen isolated in the earliest stage of its development remains obscure, the present study provided evidence that erythropoiesis in the embryonic mouse spleen was indigenous to this organ and did not result from colonization of erythroid precursors originating in the liver.

Animals↗
PubMed1998

[Prognosis of residual spleen after partial splenic embolization for the treatment of hypersplenism in cirrhosis].

The aim of this study was to elusidate the change in residual spleen volume after partial splenic embolization (PSE) in 43 cirrhotic patients with marked hypersplenism. Residual spleen volume was indicated as the rate (%) of residual spleen to initial spleen before PSE. Furthermore, the platelet count after PSE was observed in 23 patients followed up for 2 years. Residual spleen volume in patients with infarction rates of more than 80% (group A) had been maintained within 20 % even after 2 years, while they had obviously increased during the early stage after PSE in patients with infarction rates under 80% (group B), especially in patients with lower infarction rates (under 60%). Mean platelet count improved significantly in both groups after PSE (p < 0.001, respectively), but increased more in group A than in group B (p < 0.01). High fever and abdominal pain were observed in all cases of PSE. Other adverse effects such as pleural effusion and ascites that were frequent in group A were transient. These results suggest that PSE performed with a high infarction rate of the spleen provides effective, long-lasting results in the treatment of hypersplenism in cirrhosis.

Embolization, Therapeutic↗
PubMed1993

Spleen in sickle cell anemia: comparative studies of Nigerian and U.S. patients.

Anecdotal reports have attributed persistent splenomegaly in African sickle cell anemia (SS) patients to the effects of malaria. However, no comparative studies of patients in malarial and nonmalarial regions have been conducted, and few studies of malaria antibody titers have been reported. In the present study, age- and sex-matched Nigerian patients (n = 310), while it was found only in 8% of U.S. patients (n = 100) from Georgia. There was significant linear correlation between spleen size and Hb levels and with serum immunoglobulins in the Nigerian group. However, serum complement levels (C3 and C4) were not affected by spleen size. In both groups, patients with splenomegaly had fewer circulating pitted red cells than their counterparts without splenomegaly. The mean +/- SE of IgG-specific malaria antibody titer among the Nigerian patients without palpable spleens was 9,386 +/- 2,036; 9,334 +/- 2,980 in those with spleens between 1 and 5 cm, 16,201 +/- 4,502 in those with spleens between 6 and 10 cm, and 22,445 +/- 8,456 in those with spleens above 10 cm. Coexistent alpha-thalassemia did not influence the prevalence of splenomegaly among the Nigerian SS patients. This study provides additional evidence that malaria plays a significant role in the persistence of splenomegaly in African patients.

Adolescent↗