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PubMed1983

Heart and spleen "twin grafts" in rats: IV. Influence of donor spleen cell mass on allograft survival.

Heart and spleen twin grafts from LEW to ACI rats may survive permanently, whereas those grafted from ACI to LEW rats do not. This strain difference in graft acceptance was analyzed quantitatively by transplanting one to three ACI spleens into LEW rats in order to compensate for the relatively small size of ACI spleens (Fig. 1). Under these conditions permanent graft survival was not observed in LEW recipients. However, during host splenectomy 3 days after transplantation, a nonimmunological factor was observed. The transplanted ACI spleens showed congestion and infarctions, while in the LEW to ACI transplant model the LEW spleens did not. This observation could be explained by the size of the vascular pedicle in ACI spleens. Although no problem was encountered immediately after completing the anastomoses, allogeneic spleens react by increasing in size, to such an extent that their size exceeds the capacity of the smaller vascular pedicle in ACI rats and results in congestion. Hence, the concept is formulated that early compromise of hemodynamics on a nonimmunological base may determine the fate of ACI spleen graft before immunological factors have a chance to become effective.

Animals↗
PubMed1994

Beta 2-integrin dependent aggregate formation between LB T cell lymphoma and spleen cells: assessment of correlation with spleen invasiveness.

LB is an aggressive T cell lymphoma which rapidly invades the spleen and lymph nodes of BALB/c mice after s.c. inoculation. We previously reported that mAb directed against the beta 2 chain of the leukocyte function-associated antigen-1 (LFA-1) adhesion molecule (CD18) blocked the invasion of LB cells into the spleen but not into the lymph nodes. The same antibody also blocked in vitro aggregate formation between normal spleen cells and LB cells. However, aggregate formation between normal lymph node cells and LB cells was not detected, regardless of ratio. In an attempt to evaluate the association between aggregate formation and tumor invasion of the lymphoid organs, we have now extended the study. Intravenous injection of anti-CD18 mAb, which blocked spleen invasion by LB cells, also blocked the formation of ex vivo aggregates, spontaneously generated in spleen, but not in lymph node, cell suspensions of BALB/c mice s.c. inoculated with LB cells. In contrast, mAbs unable to block spleen invasion were ineffective inhibitors of both in vitro and ex vivo aggregate formation between spleen and LB cells. Spleens of nude mice that did not provide a supportive environment for lymphoma invasion, were also deficient in target cells forming aggregates with LB cells. In line with this observation, enriched T cells formed more aggregates with LB cells than did enriched non-T cells, indicating the lymphoma's preferential binding to splenic T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

[Changes in cyclic nucleotides and its enzymes in the spleen and plasma of similar spleen deficiency rats induced by rhubarb and the readjusting function of yiqi jianpi decoction].

In order to investigate the nature of Spleen deficiency and the mechanism of immunodepression due to Spleen deficiency and explore the pharmacological action of Chinese drugs of Yiqi Jianpi decoction (YQJP), the authors had established the rats model by administration Rhubarb. The preliminary results demonstrated that the symptoms manifested in rats were similar to those of Spleen deficiency syndrome. The changes of cyclic nucleotides in the spleen and plasma were unanimous. The cAMP level and the ratio of cAMP/cGMP decreased significantly while cGMP level increased significantly. Adenylate cyclase (AC) activity in the spleen reduced remarkably while cAMP-PDE activity had little changes. After the administration of YQJP, the symptoms of Spleen deficiency improved to normal extent. YQJP elevated the cAMP level, the ratio of cAMP/cGMP and AC activity while it lowered the cGMP level. The results showed that the changes of cyclic nucleotides level and the ratio of cAMP/cGMP were important targets of Spleen deficiency and that the action of YQJP followed the change of the ratio of cAMP/cGMP. The results of this study indicated that immunodepression of Rhubarb was due to depressing AC activity and reducing the ratio of cAMP/cGMP. The readjusting action of YQJP was concerned with AC system. This study supplied Spleen deficiency and YQJP with certain data in biochemical mechanism and pharmacological function.

Adenylyl Cyclases↗
PubMed1984

[Glycosaminoglycans in the spleen of normal humans and in the spleen of subjects with chronic myeloid leukemia].

The average glycosaminoglycan content in control spleens, expressed as uronic acid, was 0.23 +/- 0.02 mg/g of dry wt; the average glycosaminoglycans content in spleens of CML patients, expressed as uronic acid, was 0.91 +/- 0.23 mg/g of dry wt. In control and in leukemic spleens the same glycosaminoglycans were present, that is hyaluronic acid, heparan sulphate, dermatan sulphate, chondroitin-4-sulphate and chondroitin-6-sulphate. However, in leukemic spleens the normal quantitative relationship between these glycosaminoglycans was greatly modified; in fact in control spleens hyaluronic acid, heparan sulphate and the chondroitin sulphates were present in almost equal proportions, whereas in leukemic spleens the chondroitin sulphate group alone represented almost 9/10 of all the glycosaminoglycans. Since this proportion is weakly modified in leukemic spleens in which the number of myeloid cells has been notably reduced after chemotherapy, we may suppose that this phenomenon is due to the very marked modifications which take place in the micro-environment of the leukemic spleen.

Chondroitin Sulfates↗
PubMed1986

Cells involved in the immune response. XXXI. The role of the spleen in the primary and secondary immune responses in the normal adult outbred rabbit: the initial localization of memory cells to the spleen and their subsequent dissemination to the thymus and peripheral lymph nodes.

Normal adult outbred rabbits were immunized intravenously (iv) with sheep erythrocytes (SRBC). At varying times thereafter, the different lymphoid organs were investigated for spontaneous and culture-induced antibody secreting cells by the aqueous hemolytic plaque-forming cell (PFC) technique. During the phase of active antibody formation (Days 3 to 30), immediate PFC, indicative of spontaneous antibody synthesis and secretion, were detected principally in the spleen. In the early postimmune memory period (Days 30 to 90), memory cells capable of generating PFC following secondary immunization in in vitro culture with SRBC were detected only in the spleen. However, by 4 months postimmunization, memory cells were detected in the thymus and popliteal lymph node (PLN) as well as in the spleen. The number of memory cells in the thymus and PLN was significantly higher by 6 months postprimary iv immunization and was even further elevated by 9 months postprimary iv immunization. Following in vivo secondary immunization by the iv injection of SRBC 2 or 6 months postprimary immunization, immediate PFC were detected in large numbers in the spleen, the bone marrow, and the blood, marginally in the PLN and not at all in the thymus. Similar results were obtained at 9 months following primary immunization with SRBC with the exception that large numbers of immediate PFC were detected in the PLN following secondary iv immunization. Following culture of these lymphoid cells for 5 days in vitro with SRBC, the thymus and PLN cells, as well as the spleen cells, generated large numbers of PFC. Since immediate PFC were never detected among the freshly isolated thymus cells whereas thymic cell cultures 6 and 9 months postprimary iv immunization invariably generated large numbers of PFC following secondary immunization in vitro, the thymus memory cells would appear to be inaccessible to particulate antigen injected intravenously; they can only be detected following activation by the antigen in culture. The PFC generated by thymus memory cells (and spleen and PLN) were totally inhibited by the inclusion of sheep anti-rabbit IgG into the PFC assay. This finding demonstrates unequivocally that the plaques induced by thymus cells, just as the plaques induced by spleen and PLN cells, are antibody mediated and not false plaques. Therefore, the thymic PFC cells must be antibody-secreting B-memory cells since T cells do not synthesize or secrete immunoglobulins.

Animals↗
PubMed1976

Pyruvate kinase isozymes in various tissues of rat, and increase of spleen-type pyruvate kinase in liver by injecting chromatins from spleen and tumor.

Pyruvate kinase [EC 2.7.1.40] in various tissues of rats was separable into seven kinds of pI-isozymes by isoelectric separation with Ampholine carrier ampholytes; pI 5.4-isozyme, pI 5.6-isozyme, pI 6.2-isozyme (2 kinds), pI 6.6-isozyme, pI 7.4-isozyme, and pI 7.8-isozyme. Some of these pI-isozymes contained bound fructose 1,6-diphosphate (FDP). The bound FDP was completely dissociated when the pI-isozymes were salted out with ammonium sulfate. In the FDP-free form, pyruvate kinase was classified into three types, liver-type (type L) of pI 6.2, muscle-type (type M) of pI 7.4, and spleen-type (type M2) of pI 7.8. The liver-type isoenzyme had two kinds of FDP-binding sites; the pI 5.6-isozyme and pI 5.4-isozyme were obtained when one and two kinds of sites were bound with FDP, respectively. The association and dissociation of FDP at both sites were reversible in the presence and absence of 0.15 M KC1 (high ionic strength). The muscle-type isoenzyme had no FDP-binding site. The spleen-type isoenzyme had two kinds of FDP-binding sites, like the liver-type isoenzyme. When the ionic strength of solutions containing the enzyme and FDP was sufficiently low, one and two kinds of the sites could bind with FDP, converting the enzyme into pI 6.6-isozyme and pI 6.2-isozyme, respectively. FDP bound with one kind of site (the 2nd site) was easily dissociable, but FDP bound with the other kind of site (the 1st site) was not. Provided that the 1st site carried bound FDP, the 2nd site was associable at high ionic strength. The liver-type isoenzyme free of FDP and the spleen-type isoenzyme bound with FDP at both sites had similar pI values of 6.2 and were not separable by isoelectric separation. Some properties of these pI-isozymes were compared. When Rhodamine sarcoma was transplanted in rats, the content of spleen-type isoenzyme in the livers increased. When rats were injected with chromatin prepared from either Rhodamine sarcoma or spleen, the content of spleen-type isoenzyme in the livers again increased. This was not observed on the injection of chromatin prepared from liver, indicating that the factor capable of controlling the gene expression was present in chromatins of sarcoma and spleen but barely or not at all in chromatin of liver.

Animals↗
PubMed1976

Graft-versus-host reactivity and renal allograft survival in rats given allogeneic spleen cells or spleen allografts.

Selective recruitment of antigen-sensitive cells (ASC) into the spleen as a method of inducing specific suppression was attempted by intravenous injection of either DA or Lewis spleen cells 24 hr before a (DA X Lewis)F1 renal allograft into a Lewis or DA recipient, either with or without a splenectomy. This led to suppression of rejection in the DA recipient and delayed rejection in the Lewis recipient. Splenectomy produced a minimal augmentation effect. Assay of graft-versus-host (GVH) reactions in (DA X Lewis)F1 rats by a popliteal node assay showed that injection of allogeneic DA or Lewis spleen cells 48 hr before the assay significantly reduced the reaction produced by node lymphocytes but not spleen lymphocytes, suggesting a loss of ASC from the lymph nodes. Lewis spleen allografts did not produce such a significant reduction in the GVH reactivity of DA node lymphocytes as intravenous Lewis cells, whereas DA spleen allografts led to an increased GVH reactivity of Lewis node lymphocytes. From these studies, it is not possible to attribute the suppression produced by the intravenous injection of allogeneic cells to selective recruitment of antigen-sensitive cells to the spleen.

Animals↗
PubMed1978

Morphological studies of the spleen in splenomegalic liver cirrhosis comparing with the spleen in idiopathic portal hypertension (so-called Banti's syndrome without liver cirrhosis).

Morphological changes of the spleen in splenomegalic liver cirrhosis (SLC) were studied. Comparisons with the normal spleen and the spleen of idiopathic portal hypertension (IPH) were made by (1) light microscopy with histometry, (2) scanning electron microscopy (SEM) with histometry, and (3) SEM of the spleen vascular replica. Histometrical studies by light microscopy showed that in both SLC and IPH, the white pulp volume was decreased in random units of splenic tissue but increased in the whole spleen, whereas the red pulp volume was increased both in random units of splenic tissue and in the whole spleen. The increase in the total volume of the white pulp was less marked in SLC than in IPH. SEM histometry demonstrated in the red pulp an increase in small venous sinuses and narrowing of the Billroth cord in SLC and IPH. Narrowing of the Billroth cord was more marked in SLC than in IPH. SEM of the white pulp showed channels formed by reticulum cells around the central artery in SLC and IPH. The channels are thought to correspond to so-called "follikuläre Fibroadenie" or periarterial fibrosis. The spleen vascular replica demonstrated open arterial termination into the tissue spaces in the Billroth cord in SLC, IPH and the normal. Venous sinuses were arranged in bundles in SLC and IPH.

Adult↗
PubMed1990

The isolated perfused rat spleen. An original method for studying the function of hepatocytes transplanted into the spleen.

The aim of this study was to assess directly the function of isolated hepatocytes 1 year after transplantation into the spleen, using an original model of isolated rat-spleen perfusion. Three specific liver functions, albumin synthesis, indocyanine-green clearance, and antipyrine oxidation, were studied. Five x 10(6) isolated hepatocytes were injected into the spleen of syngenic Wistar-Furth rats. One year later, splenectomy was performed, and the splenic pedicle was carefully isolated in order to allow a selective ex vivo perfusion for 3 hr. De novo albumin synthesis was studied by qualitatively using immunoelectrophoresis and autoradiography, and quantitatively using (35S)-methionine incorporation in albumin. De novo albumin synthesis was observed in spleens containing transplanted hepatocytes but not in controls (P less than 0.001); (35S)-methionine incorporation was significantly higher in spleens containing transplanted hepatocytes than in controls (132 +/- 67 cpm/spleen/hr vs. 14 +/- 6 cpm/spleen/hr, P less than 0.001). Antipyrine clearance was significantly higher in spleens with transplanted hepatocytes than in controls (67.4 +/- 4.9 microliters/min/g vs. 0.2 +/- 0.4 microliters/min/g, P less than 0.01). No statistically significant difference was observed with indocyanine-green clearance (4.2 +/- 6.0 microliters/min/g, vs. 5.2 +/- 5.1 microliters/min/g, P greater than 0.05); this was probably due to the absence of compartmentation between the sinusoid and biliary sectors in this model. In conclusion, using this original isolated rat-spleen perfusion model, it was directly observed that 1 year after transplantation, intrasplenic hepatocytes can perform two liver-specific functions, i.e., de novo albumin synthesis and antipyrine clearance.

Albumins↗
PubMed2000

Spleen enlargement in patients with nonalcoholic fatty liver: correlation between degree of fatty infiltration in liver and size of spleen.

Our purpose was to determine if there is an association between nonalcoholic fatty liver and spleen enlargement. Spleen volume was measured by computed tomography (CT) in 32 patients with nonalcoholic fatty liver (23 men and 9 women; age, 41.6+/-12.1, range, 22-69 years) and 34 patients with normal liver (19 men and 15 women; age, 51.1+/-16.2, range, 14-86 years). The values were compared with the patient's demographic data, the liver-to-spleen (L/S) ratio of CT Hounsefield unit measurements, and the results of liver function tests. Diagnosis of fatty liver was made if the L/S ratio was less than 1.0. The mean spleen volume was 73.0+/-24.4 cm3 (range, 21.1-106.1) in normal subjects and 141.2+/-54.1 cm3 (range, 44.1-267.3) in patients with fatty liver (P<0.0001). Multivariate linear regression analysis identified that only the L/S ratio (P<0.0001) and age (P<0.01) were significantly correlated with spleen volume. Using forward selection stepwise regression, the L/S ratio entered first (beta = -0.634) and age second (beta = -0.293). In conclusion, spleen enlargement was commonly seen in patients with nonalcoholic fatty liver, and the recognition of this association may halt further attempts to evaluate the cause of spleen enlargement.

Adult↗
PubMed1976

Enhancing effect of radioresistant spleen cells on the primary immune response against sheep RBC by mouse spleen cells in vitro.

Irradiated spleen cells cultured for 3 days, caused a stimulation of the primary in vitro immune response by normal spleen cells. These irradiated spleen cells were fractionated by velocity sedimentation and the fractions were tested for their stimulating activity. Only the macrophage enriched fractions were found to cause stimulation. The macrophages in these fractions were stuffed with erythrocytes and dead cells. The fractions enriched in thymus derived cells, had no effect on the immune response. Irradiated spleen cells cultured for 24 hours caused inhibition. It has not yet been determined whether this inhibition was due to some transient change in the macrophage population during incubation. The stimulating effect by the irradiated spleen cells from SPF mice was strongly reduced, which at least partly could be ascribed to the naturally occurring low number of macrophages in the spleens of these mice.

Animals↗
PubMed1989

In vivo and in vitro synergistic antitumor effect of interleukin-2-cultured tumor-bearer spleen cells and immune fresh spleen cells.

The synergistic antitumor effect of interleukin-2(IL-2)-cultured tumor-bearer spleen cells (cultured lymphocytes) and immune fresh spleen cells was examined. Tumor-bearer cultured lymphocytes were obtained by culturing BALB/c spleen cells from syngeneic MOPC104E-tumor-bearing mice for 11 days with crude IL-2 and a soluble tumor extract. These cultured lymphocytes had weak antitumor activity when transferred i.p. into tumor-bearing mice that had been inoculated i.p. with 10(5) tumor cells 5 days previously. Immune fresh spleen cells, obtained from mice in complete remission after the treatment with cyclophosphamide, also had weak antitumor activity when transferred at the same schedule. The cultured cells and the fresh cells, mixed together before transfer, significantly augmented the therapeutic effect. At least 1 x 10(7) tumor-bearer cultured lymphocytes and 4 x 10(7) immune cells were needed for the synergistic effect. A tumor-specific combination was needed for both cultured and fresh cells. The effective subpopulation of tumor-bearer cultured lymphocytes was a cytotoxic one from an Lyt2+ precursor, and that of the immune fresh spleen cells was noncytotoxic, Lyt1+ and Lyt2+ T-cells. A similar synergistic effect was also observed during in vitro coculture of tumor-bearer and immune cells. Cytotoxicity, as assessed by the 51Cr-release test, of tumor-bearer IL-2-cultured lymphocytes was maintained most effectively after 3 or 4 days of culture without IL-2 when the lymphocytes were cocultured with immune fresh spleen cells and tumor cells.

Animals↗
PubMed1986

[Sonographic determination of spleen size: normal dimensions in adults with a healthy spleen].

Sonography can rapidly and reliably help to determine the size by the spleen. To standardise the sonographic dimensions of the healthy spleen, we effected sonographic examination of 793 female and male patients aged between 17 and 82 years with a healthy spleen. In 95% of the patients the length of the spleen was less than 11 cm, the breadth below 7 cm and the thickness less than 5 cm. The weight of the spleen as determined via the rotation ellipsoid formula was below 190 g in 95% of the patients. Whether or not a spleen larger than standard signals an acute disease can be clinically assessed only on the basis of a synopsis of all findings.

Adolescent↗
PubMed1982

Spleen cells from adult mice given total lymphoid irradiation or from newborn mice have similar regulatory effects in the mixed leukocyte reaction. I. Generation of antigen-specific suppressor cells in the mixed leukocyte reaction after the addition of spleen cells from adult mice given total lymphoid irradiation.

We added spleen cells from adult BALB/c mice treated with total lymphoid irradiation (TLI) to the mixed leukocyte reaction (MLR) using a variety of responder and stimulator cells. The spleen cells nonspecifically suppressed the uptake of [3H]-thymidine and the generation of cytolytic cells regardless of the responder-stimulator combination used. We also examined the effect of the spleen cells on the generation of antigen-nonspecific and antigen-specific suppressor cells in the MLR. The experimental results suggest that the spleen cells from TLI-treated mice inhibit the generation of nonspecific suppressor cells, but do not inhibit the generation of antigen-specific suppressor cells. Thus, alloantigenic stimulation of normal responder cells in vitro in the presence of spleen cells from TLI-treated mice generates large numbers of antigen-specific suppressor cells, but few cytolytic cells or nonspecific suppressor cells. Similar nonspecific inhibition of the MLR was observed with neonatal spleen cells. This in vitro system provides a regulatory model for the induction and maintenance of tolerance in vivo, in which adult mice given TLI or neonatal mice accept allogeneic bone marrow transplants without graft-vs.-host disease.

Animals↗
PubMed2006

[Pharmacokinetic characteristics of ferulic acid in patients with different syndromes of deficiency of spleen qi, stagnation of liver qi and spleen deficiency, and excess of stomach heat].

OBJECTIVE: To investigate the nature of syndrome of traditional Chinese medicine by means of pharmacokinetic (PK) method. METHODS: Twenty-one healthy volunteers, 20 patients with syndrome of stagnation of liver qi and spleen deficiency, 22 patients with syndrome of deficiency of spleen qi and 19 patients with syndrome of excess of stomach heat were included and administered to take Jiawei Xiaoyaosan Recipe (JWXYSR). The serum PK parameters of ferulic acid (FA) were examined by high performance liquid chromatography (HPLC) method. RESULTS: The absorption rate constant (alpha) and the elimination rate constant (beta) were both decreased while the apparent first-order absorption constant (K(a)) was enhanced significantly in the patients with syndrome of deficiency of spleen qi; the alpha, beta and Ka were all reduced in the patients with syndrome of stagnation of liver qi and spleen deficiency; the beta and K(a) were increased in the patients with syndrome of excess of stomach heat, as compared with the corresponding PK parameters in the healthy volunteers (P<0.01). CONCLUSION: The PK analysis of FA in the patients with syndrome of deficiency of spleen qi shows that the absorption rate is accelerated, and both the distribution and elimination rates are slowed down. The absorption, distribution and elimination rates of AF are all slowed down in the patients with syndrome of stagnation of liver-qi and spleen deficiency, while the absorption and elimination rates of AF are both accelerated in the patients with syndrome of excess of stomach heat. There are obvious differences in the PK characteristics among these three syndromes.

Adult↗
PubMed1986

[Autotransplantation of the spleen. A new possibility in the conservative surgery of the spleen].

Conservative surgery to spleen is an ancient concept brought up-to date by improved knowledge of its fundamental roles in immunity and anti-bacterial defences. Suture of spleen and partial splenectomy ensure the best possible functional results but have technical limitations resulting frequently in splenectomy to provide hemostasis. Data from clinical and experimental studies and reports in the literature have demonstrated that autotransplantation of spleen is a simple, safe and effective method for preventing the true dangers of asplenia. Optimal results from autotransplantation of spleen are obtained when the injured organ is broken into small fragments which are then implanted into small spaces fashioned in the greater omentum. Clinical and biological tests to evaluate functional value of these transplants have shown that results approach those of a normal or sutured spleen. It is concluded that this procedure, which completes other conservative methods of splenic surgery, should definitely exclude hemostasis splenectomy from therapy of injuries to spleen.

Animals↗
PubMed1975

Immune complexes in the spleen. Replacement of immune complexes trapped in spleen follicles by new immune complexes from the circulation.

The fate of intravenously injected 125I-BGG-anti-BGG in the spleen of mice was studied using autoradiography. Part of the labelled immune complexes was trapped in the follicles of the spleen as could be expected. In a first experiment it was found that injections with unlabelled immune complexes were followed by a partial release of the labelled immune complexes from the follicles. In a second experiment unlabelled immune complexes retained in spleen follicles appeared to inhibit the trapping of intravenously injected labelled immune complexes to some degree and for some time. The conclusion was drawn from these experiments that immune complexes, which normally remain in part of the lymphoid follicles for a long period, may be replaced by new immune complexes from the circulation. This seems important since trapping in lymphoid follicles of antigen complexed by antibody is the only known mechanism by which small amounts of antigen may be preserved in the body for a long time after the initiation of antibody production. The bulk of antigen and antigen-antibody complexes is removed by phagocytosis followed by destruction. It appeared also that, although all spleen follicles in the mouse spleen is able to retain the complexes for a longer time. Possible explanations for these individual differences between the follicles of one spleen are discussed.

Animals↗