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Induction of cytokines in human peripheral blood and spleen cells by the Mycoplasma arthritidis-derived superantigen.

Recently, the mitogenic effects of the Mycoplasma arthritidis supernatant, MAS, and the induction of interferon-gamma (IFN-gamma) and interleukin-6 (IL-6) by MAS have been described. In the present series of experiments we investigated human peripheral blood mononuclear cells (PBM) and human spleen cells with respect to their production of these and other cytokines. In human spleen cell cultures and PBM, MAS induced the synthesis of interleukin-1 alpha (IL-1 alpha) and IL-1 beta. Both interleukins were secreted faster and in higher amounts by PBM. IL-6 was also induced by MAS in PBM and human spleen cells. The amounts of IL-6 measured by ELISA were higher in PBM, whereas the biological activity of IL-6 was higher in spleen cell cultures. T-cell products such as IL-2, IL-4, and IFN-gamma were also induced by MAS in PBM and spleen cells. The kinetics of IFN-gamma and IL-4 induction were negatively correlated. In PBM we found low levels of IL-4 and high IFN-gamma induction, whereas in spleen cells high titers of IL-4 and low IFN-gamma titers were observed. Collectively, our results indicate that MAS induces different networks of cytokine interactions depending on the organ from which the cells are derived.

Antigens↗

[Accessory spleen: ultrasonographic and tomographic characteristics].

The failure of fusion of splenic tissue results in the formation of accessory spleens. This entity normally appears in post-mortem examinations. The purpose of this work was to determine the incidence of the accessory spleen and to compare the ultrasonographic and tomographic features of the accessory spleen and the main spleen in a group of one thousand patients affected with several abdominal pathologies. Five hundred of these patients were studied by ultrasonography and five hundred patients by computed tomography. The ultrasonographic and tomographic features of the accessory and main spleen were similar. Its diagnosis is specially important in certain groups of patients with hematologic disease or abdominal trauma with splenic tear. This is due to the fact that the hypertrophy of the accessory spleen can produce a relapse of the disease.

Congenital Abnormalities↗

[Wandering spleen].

The spleen is well fixed below the left side of the diaphragm. Wandering spleen is a rare condition of unknown pathogenesis. The wandering spleen is most often localized in the lower abdomen or pelvis. The diagnosis may be difficult if wandering spleen is not suspected. Often a wandering spleen can be palpated in the lower abdomen. In the rare cases of torsion of the splenic vascular pedicle, wandering spleen becomes symptomatic, and splenectomy should be performed. We report a case of a 20-year-old female treated with splenectomy because of torsion of the vascular pedicle.

Adult↗

[Controlled study of needle warming therapy and electroacupuncture on simple obesity of spleen deficiency type].

OBJECTIVE: To compare therapeutic effects of needle warming therapy and electroacupuncture on simple obesity with spleen deficiency. METHODS: Sixty-eight cases of simple obesity with spleen deficiency, including water-dampness retention due to spleen deficiency, qi-deficiency of the lung and spleen, yang-deficiency of the spleen and kidney, were randomly divided into a needle warming therapy group (n = 36) and an electroacupuncture group (n = 32). Zhongwan(CV 12), Shuifen (CV 9), Qihai (CV 6), Zhongji (CV 3), Tianshu (ST 25), Shuidao (ST 28), and so on were selected as main acupoints in the both groups. Their therapeutic effects and body mass indexes were observed. RESULTS: The total effective rate was 88.9% in the needle warming therapy group and 71.9% in the electroacupuncture group with a significant difference between the two groups (P < 0.05); and there was a significant difference between the two groups in decrease of body mass index (P < 0.05). CONCLUSION: Needle warming therapy has definite and long-term therapeutic effect on simple obesity with spleen deficiency.

Acupuncture Points↗

Wandering spleen with torsion and gastric volvulus.

Wandering spleen, defined as a spleen without its usual peritoneal attachments, is a rare entity, particularly in children. It usually occurs in those aged 20 to 40 years, and most cases occur in women. Patients usually become symptomatic when torsion of the splenic pedicle occurs. Gastric volvulus, like wandering spleen, is also related to anomalies of intraperitoneal visceral attachments. However, cases of wandering spleen associated with gastric volvulus are rare. We report a case of wandering spleen with torsion and gastric volvulus. The patient was a 4-year-old girl who presented with acute intractable vomiting and abdominal pain. Exploratory laparotomy was performed under the impression of wandering spleen with torsion. The gastric volvulus was found intraoperatively. Following splenectomy and gastropexy, Haemophilus influenza type b and pneumococcus vaccination and prophylactic antibiotics were given. She recovered uneventfully and had no signs of illness or ongoing infection at 1-year follow-up after the operation.

Child, Preschool↗

Effects on spleen colony-forming unit self-renewal after retroviral-mediated gene transfer of multi-colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, or granulocyte colony-stimulating factor.

C57BL/6 mice were established to constitutively produce multi-colony-stimulating factor (multi-CSF), granulocyte-macrophage colony-stimulating factor, or granulocyte colony-stimulating factor by transplantation with post-5-fluorouracil-treated syngeneic marrow cells infected with retroviral vectors bearing the corresponding growth factor complementary DNAs. At 2-4 weeks after transplantation, these mice had a 2-7-fold increase in spleen colony-forming unit (CFU-S) numbers when compared to control animals transplanted with MPZipNeo-infected marrow cells. Most of the CFU-S in the former animals were located in the spleen, whereas those of control mice were found in the marrow. The increase in total CFU-S content in recipients of CSF-infected mice was not due to an increase in self-renewal ability but rather to the recruitment of more primitive cells, as there were no differences in CFU-S content of spleen colonies generated from marrow cells of either group. Neither were there any differences in the cellular composition of these spleen colonies or in the size or distribution of cell types in secondary spleen colonies generated from these spleen colonies, suggesting the inability of any of the three CSFs to alter the differentiation pattern of CFU-S.

Animals↗

[Malignant lymphoma of the spleen. Histological and immunohistochemical studies of morphology and differential diagnosis].

450 splenectomy specimens showing involvement by all save a few very infrequently occurring types of malignant lymphomas (ML) recognized by the updated Kiel classification of ML were investigated by conventional histologic and immunohistochemical methods. The results confirm and augment the findings of previous studies and facilitate a comparison of infiltration patterns of different ML in the spleen. These studies in conjunction with immunohistochemical detection of neoplastic cells may thus contribute to the diagnosis of minimal, i.e. early, splenic infiltration by ML and to the differential diagnosis of ML with advanced splenic involvement. Initially, most low grade NHL lead to nodular involvement of the splenic white pulp which may evolve into larger tumor nodules and/or diffuse red pulp involvement by invasion of adjacent red pulp structures. As a rule, the infiltrates are angiotropic, i.e. neoplastic cells accumulate in the vicinity of arterial and venous blood vessels both in the white and in the red pulp. Sinus involvement is frequently associated with leukemic generalisation of the neoplasm. High grade NHL are also localized predominantly in the splenic white pulp. However, their intrasplenic spread is characterized by the formation of large nodular and/or diffuse infiltrates which may efface the splenic architecture. Hodgkin lymphomas (HL), in contrast, cause coalescing tumor nodules which show expansive growth rather than progressive infiltration of the splenic parenchyma. These infiltration patterns of ML in the spleen are a constant finding. In conjunction with cytologic features and immunophenotype of the neoplastic cells they thus constitute reliable criteria for the differential diagnosis of ML in the spleen, although their anatomical and functional basis has not yet been fully elucidated. B and T cell lymphomas initially tend to show selective involvement of the original B and T cell areas of the spleen. Most high grade ML exhibit a similar behavior, although the size of the splenic lesions usually does not permit an exact identification of the ML's primary manifestation in the spleen. They thus exhibit a "homing phenomenon" to the two large lymphoid compartments of the spleen which is most conclusively illustrated by the "organoid" ML such as CB-CC or T zone lymphoma. This behavior has been interpreted to reflect the histogenesis of the neoplastic cells of the ML under study. In addition, specialised types of accessory cells such as CD35+ FDC and CD1/S100+ IDRC appear to be essential for the creation of conditions which are suitable for B and T lymphocytes, respectively. Progressive infiltration by neoplastic cells will lead to destruction of the normal microenvironment, i.e. alterations of FDC networks.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigens, CD↗

Relationship between large and small tumor-binding cells in the spleen and bone marrow.

By employing a distinctive feature of natural killer (NK) cells, i.e., spontaneous target cell binding, the present study aimed to follow a relatively large cohort of target-binding cells (TBC), subdivided according to size and the presence of the radioautographically labelled nucleotide, tritiated thymidine, incorporated during a 1- or 6-hour exposure period. Labelling among all TBC in the spleen was 5% by 1 h after a single injection of the isotope and this value did not change significantly after 6 h of isotope exposure. There was an insignificant increase in the labelling index of spleen-localized, labelled, large TBC throughout and beyond the isotope exposure period for at least 48 h, concomitant with a significant increase in the labelling index of spleen-localized, small TBC during the same period. In the bone marrow, small TBC showed only 2% labelling by 1 h after a single injection of isotope, while 21% of large TBC in that organ were synthesizing DNA during the same period. The results are consistent with a precursor-product relationship between large and small TBC within the bone marrow but not the spleen, and with a bone marrow-to-spleen migration of small (+/- large) TBC. Moreover, a minor population of large TBC was detected in the spleen with kinetic characteristics distinct from those of the bone marrow.

Animals↗

Effects of 60Co gamma-irradiation of mice on the temporal changes of acid phosphatase activity in spleen and liver.

Acid phosphatase activity and protein content of spleen and liver, and organ weight of whole-body 10 Gy 60Co gamma-irradiated mice were measured every four hours during a 24-hour period. In irradiated mice, in comparison with those non-irradiated, increased acid phosphatase activity in spleen related to both 1 mg of protein at 20.00I, 04.00, 08.00, 12.00, 16.00 and 20.00II and 1 g of fresh tissue at 20.00I, 08.00, 12.00, 16.00 and 20.00II; decreased weight of spleen and protein amount in spleen during the whole 24-hour period, as well as fluctuations in all the parameters measured in spleen, except the level of protein related to 1 g of fresh tissue, were observed. In irradiated mice, compared with the controls, the increased acid phosphatase activity in liver calculated per both 1 mg of protein at 24.00, 08.00 and 16.00 and 1 g of fresh tissue at 08.00 and 16.00; the decreased protein concentration in liver related to 1 g of fresh tissue and the whole organ weight at 12.00, as well as temporal changes in the protein level in liver expressed per 1 g of fresh tissue, were found. 60Co irradiation of mice influenced the acid phosphatase activity and protein concentration in liver are less than in spleen.

Acid Phosphatase↗

Immune suppression induced by protoscoleces of Echinococcus multilocularis in mice. Evidence for the presence of CD8dull suppressor cells in spleens of mice intraperitoneally infected with E. multilocularis.

Immunoregulatory states induced by i.p. inoculation with the metazoan parasite Echinococcus multilocularis in the murine system were investigated. Proliferative responses and IL-2 production induced by Con A in spleen cells from BALB/c mice were significantly depressed at an early stage after infection with E. multilocularis protoscoleces (PSC). Addition of plastic-adherent cells from normal syngeneic mice to the nonadherent spleen cells from infected mice did not restore the depressed Con A responsiveness. On the other hand, exogenous IL-2 reconstituted completely the proliferative responses to Con A. Flow cytometry analysis revealed that CD4- CD8+ cells with a low density of CD8 Ag (CD8dull cells) increased in spleens from infected mice 2 weeks after inoculation. Addition of the spleen cell subpopulation containing the CD8dull cells, but not that depleted of the CD8dull cells, to normal spleen cells resulted in marked suppression of the Con A responses. These findings suggest that the CD8dull cells detected in spleens of mice inoculated with E. multilocularis PSC may play a key role in the suppressive regulation of immune responses. The relevance of the immune suppression seen in the early stages of experimental infection with E. multilocularis PSC to the eventual establishment of a host-parasite relationship is discussed.

Animals↗

In vitro mitogenic stimulation of murine spleen cells by herpes simplex virus.

Spleen cells of B6 mice not previously immunized were induced to DNA synthesis by supernatants from HSV-infected tissue culture. The stimulatory principle could be passed through a 45-micrometer filter and sedimented at 100,000 x G. It was abolished by UV light, heating at 56 degrees C, and by an anti-HSV serum. The possibility that the observed stimulation was caused by LPS was therefore excluded, and there was a-so no indication of mycoplasma contamination. Partial purification of spleen cells from macrophages resulted in an increased stimulation by HSV. From experiments with nylon columns, anti-theta antibody, and nude mice it was concluded that HSV acted as a B cell mitogen. Strains of both HSV types 1 and 2 were stimulatory for B6 spleen cells. Of nine freshly isolated HSV strains with identical passage history (twice in HEF) four were strongly stimulatory, three showed a moderate stimulation, and two did not stimulate. Spleen cells from A/J and DBA/2 mice were stimulated to the same extent by HSV (WAL) as spleen cells from B6 mice. No viral replication was demonstrable in B6 spleen cell cultures stimulated for DNA synthesis by HSV. Thus our study demonstrates induction of cellular DNA synthesis in B lymphocytes by HSV which is abolished by inactivation of the virus.

Animals↗

[Extracorporeal connection of heterologous spleen (ECHS) in the combined intensive therapy of sepsis].

Biohemosorption by means of extracorporeal connection of heterogeneous spleen renders not only powerful detoxic action, but intensive immunomodulation action as well. Swine spleen used for biohemosorption possess high bacterisorptive and immunomodulating potential. The cases of persistent course of disease, development of antibacterial therapy, grave condition of a patient serve as an indication for application of extracoproreal connection of heterogeneous spleen within the complex of intensive therapy. During 1989 in the hospital were treated 9 patients with osteomyelitis and extensive suppurative foci of soft tissues of the locomotor apparatus, complicated by severe sepsis. Those patients were applied to totally II extracorporeal connections of heterogeneous spleen and 8 biohemosorptions by means of heterogeneous spleen sections. In general, intensive therapy with application of extracorporeal connection of heterogeneous spleen was effective enough. All patients with no exception left hospital in satisfactory condition in 28-56 days after the beginning of treatment.

Adult↗

Ultrasonographic-anatomic correlation and imaging protocol for the spleen in anesthetized dogs.

Sonographic and/or anatomic observations were made of the spleen in 27 dogs. Anatomic studies were used to establish precise correlations between the gross anatomic features of the organ and its ultrasonographic image. In 8 anesthetized dogs, ultrasonographic images of the spleen were made in dorsal, transverse, and sagittal planes. When it was incident to the ultrasonic beam, the splenic capsule was represented by a fine echogenic line that defined the boundaries of the organ. The splenic substance had a uniformly mottled echogenicity apart from the anechoic lumen of the splenic venous rami, which were detected at and near the hilus of the spleen. Less regularly, splenic arterial rami were detected at the hilus, but not within the splenic substance. Dorsal and transverse images were made with the ultrasonic transducer perpendicular to the left thoracic and abdominal wall at the 11th intercostal space and caudoventrad to it. Sagittal images were produced with the transducer's face directed craniad, placed parallel to the left lateral abdominal wall, and pushed under the costal arch. The adoption of such an ultrasonographic imaging protocol ensures that all of the spleen is inspected. A definitive opinion can then be given as to whether the spleen is normal or abnormal. Pathologic changes in the spleen must also be differentiated from changes in adjacent organs or structures.

Animals↗

[Liver regeneration and immune system--morphological and cytochemical studies of activated spleen cells during the liver regeneration after partial hepatectomy].

Morphological and cytochemical changes were investigated in spleen cells after 70% hepatectomy in mice. During liver regeneration after the hepatectomy, the spleen weight gradually rose to a peak at 6 day. In the spleen, the number of POD-positive myelocytic cells and NCAE-positive granulocytic cells also reached a peak 4 days after the operation and then decreased. On the other hand, ANBE-positive monocytic cells gradually increased up to 9 day and didn't decrease for this period. On day 9 of the culture, the boundary between the red and the white pulps of the spleen became unclear. In this spleen, the clusters of blast cells were sporadically observed. Splenic T cells cocultured with nonparenchymal adherent normal liver cell or nonparenchymal adherent normal liver cell supernatant developed into granulocyte colonies in earlier periods and monocyte colonies in later periods. These findings suggest that the factors released from liver cells may regulate strictly spleen cell activation. Blast cell formation in the culture with nonparenchymal adherent normal liver cell supernatant was amplified by anti interferon (alpha + beta) antibody. These facts indicate that the functional network of cytokines is formed by the interaction of various cytokines (IL-1, IL-6, CSF, IFN, etc.) in nonparenchymal adherent normal liver cell supernatant.

Animals↗

Human spleen and peripheral blood lymphocytes activated by interleukin-2 have similar phenotypic and functional characteristics.

Phenotypic markers and cytotoxic function were monitored in cultures of normal human mononuclear cells obtained from peripheral blood or spleen and stimulated by recombinant interleukin-2 (IL-2; 1,500 U/ml). Fresh spleen cells contained less than 5% natural killer (NK) cells (CD3-NKH1+), which increased about threefold after activation with IL-2. In both spleen and peripheral blood cultures, T cells with the NKH1 marker showed the highest relative increment among all cell types studied. Lymphokine-activated killer (LAK) cells from peripheral blood and spleen displayed very similar cytotoxic activity against K562, Daudi, and COLO carcinoma cell lines. Killing of the three targets peaked at 7 days of culture. Antibody-dependent cell cytotoxicity against a B-cell line was mediated by both circulating and splenic LAK cells from 2 to 14 days of culture. Cell sorting experiments showed that K562 targets were killed by both CD5+NKH1+ and CD5-NKH1+ cells whereas Daudi targets are only killed by CD5-NKH1+ activated NK cells from both spleen and peripheral blood. In summary, human spleen LAK cells have similar phenotypic and functional properties to circulating LAK cells, and they may be used for adoptive immunotherapy of human cancer.

Antigens, Differentiation↗

Migration of stem cells and progenitors between marrow and spleen following thiamphenicol treatment of mice.

Recovery of hemopoiesis was studied after a 3-day treatment with the antibiotic thiamphenicol (TAP). A contrasting behavior of the spleen colony-forming units (CFU-S), granulocyte-macrophage colony-forming units (CFU-GM), erythroid burst-forming units (BFU-E), and erythroid colony-forming units (CFU-E) numbers in the bone marrow versus those in the spleen was found. Whereas the cell numbers reached nadirs in the marrow, they peaked 30 to 100-fold above control values in the spleen on day 4. Simultaneously the number of CFU-S, BFU-E, and CFU-GM, but not of CFU-E, increased drastically in the peripheral blood. The tritiated thymidine kill of the splenic CFU-S was too small to explain the endogenous splenic production of these cells. A quantitative analysis further revealed that an effective erythropoiesis was established in the spleen. As a consequence, the first part of a reticulocytosis was mainly due to the splenic contribution, whereas the second part predominantly originated from a delayed marrow erythropoiesis. In contrast, the CFU-GM of the spleen did not effectively differentiate into granuloid precursors. The bulk of the granuloid production occurred in the marrow. The best explanation for these results is a net migration of CFU-S, BFU-E, and CFU-GM from the marrow to the spleen during early recovery, and a back-migration of CFU-GM to the marrow later in the recovery phase. These observations indicate a link between migration of hemopoietic cells and their differentiation at the two hemopoietic sites.

Animals↗

Mast cells contain spleen-type prostaglandin D synthetase.

Prostaglandin D synthetase activity in the cytosol (100,000 x g, 1-h supernatant) fraction of peritoneal mast cells of adult rats (105.0 nmol/min/mg protein) was the highest among such activities in various rat tissues and cells. As judged by the absolute requirement for glutathione for the reaction (Km = 300 microM), the Km value for prostaglandin H2 (200 microM), and insensitivity of the activity to 1 mM 1-chloro-2,4-dinitrobenzene, the enzyme in mast cells was similar to rat spleen prostaglandin D synthetase and differed from rat brain prostaglandin D synthetase or glutathione S-transferase, all of which catalyze the isomerase reaction from prostaglandin H2 to prostaglandin D2. In immunotitration analyses, the activity in mast cells showed a titration curve exactly identical with that of the purified spleen-type enzyme and almost completely absorbed by an excess amount of antibody against this enzyme, but it remained unchanged after incubation with antibodies against the brain-type enzyme and glutathione S-transferase isozymes thus far purified. In Western blot after two-dimensional electrophoresis of crude extracts of mast cells, a single immunoreactive spot was observed with antibody against the spleen-type enzyme at the same position as that of the purified enzyme (Mr = 26,000, pI = 5.2). Furthermore, the immunoreactive protein obtained from mast cells showed the same peptide fingerprints as those of the purified spleen-type enzyme, after partial digestion with Staphylococcus aureus V8 protease or trypsin. In immunoperoxidase staining, the immunoreactivity of the spleen-type enzyme was found in the cytosol of tissue mast cells in various organs such as thymus, intestine, stomach, and skin of adult rats. These findings indicate that prostaglandin D2 is produced by the spleen-type synthetase in mast cells of various tissues.

Animals↗

Previously unrecognized functions of the spleen: development and maintenance of immune competence and regulation.

To examine the influence of the spleen on the development and function of the immune system, the effects of the inborn asplenia in Dh/+ mice were studied and compared with those of neonatal and postnatal splenectomies. The antibody responses to particulate and soluble antigens in Dh/+ mice were weaker than those in normal controls. This was correlated with the inability of Dh/+ T-lymphocytes to cooperate with B cells in cell-transfer experiments. A defective helper function was also found in T-cells of neonatally splenectomized mice, but it could be restored partly by delaying the removal of spleen until 6 days after birth and totally by infusing autologous spleen cells immediately after splenectomy. By contrast, transfer of spleen cells to Dh/+ mice did not restore the helper function of their T-lymphocytes. Unlike their defective humoral immunity, the cellular immune responses of Dh/+ mice are normal as expressed in their ability to reject foreign grafts and to be contact-sensitized by chemicals. Thus, the presence of the spleen at birth is essential for the development of helper T-cells but not cytotoxic or effector T-cells. Furthermore, evidence is reviewed for the splenic influence on the capacity of other lymphoid organs to trap particulate antigens and for the role of the spleen in the maturation of suppressor T-cells throughout the life span.

Age Factors↗