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Spleen volume varies with colony size and parasite load in a colonial bird.

Comparisons across bird species have indicated that those more exposed to parasites and pathogens invest more in immunological defence, as measured by spleen size. We investigated how spleen volume varied with colony size, parasite load and an individual's colony-size history in the cliff swallow, Petrochelidon pyrrhonota, a colonial passerine bird of North America. We used a sample of over 1700 birds that had all died during a period of inclement weather in 1996. We experimentally manipulated ectoparasitism by fumigating nests in some colonies prior to the bad weather. Birds from parasite-free colonies had significantly smaller spleens than those from naturally infested sites; spleen volume did not differ between the sexes and did not vary with age. Mean spleen volume increased significantly with the colony size at a site prior to the bad weather in 1996 and at the site in 1995, both measures of colony size being indices of ectoparasitism at a site. An individual's history of breeding-colony size (defined as the average colony size it had occupied in years prior to 1996) had no association with its spleen size. The results are consistent with parasite-induced splenomegaly whenever birds are exposed to large numbers of ectoparasites. The results do not support spleen size as being a signal of differential life-history investment in immunological defence among individuals and thus run counter to interpretations from recent cross-species comparisons.

Age Factors↗

Splenic blood flow and intrasplenic platelet kinetics in relation to spleen volume.

The relationship between the splenic blood flow and the intrasplenic platelet kinetics on the one hand, i.e. the two factors which govern the size of the exchangeable splenic platelet pool, and the spleen size on the other were assessed in 21 patients afflicted with haematologic disorders and variable splenomegaly. The splenic blood flow and intrasplenic platelet kinetics were measured using 111In-labelled platelets and compartmental analysis of their equilibration between circulating blood and splenic pool; the spleen size was determined by scintigraphy using 99mTc-labelled stannous colloid. Significant correlations were recorded between the spleen size and the splenic platelet pool size (r = 0.76; P less than 0.001) and between the spleen size and the splenic blood flow (r = 0.56; P less than 0.01). Splenic perfusion decreased significantly with increasing spleen size, but there was no relationship between the spleen size and the intrasplenic platelet transit time. However, an association was present between splenic perfusion and intrasplenic platelet transit time (r = -0.44; P less than 0.05). It is concluded that the splenic blood flow is the major determinant of the size of the exchangeable splenic platelet pool in splenomegalic states, and that the determination of spleen size using 99mTc-scintigraphy gives a rough estimation of the pool size. Splenic perfusion appears to be one of the factors which determine the intrasplenic platelet transit time.

Adult↗

Spleen neoangiogenesis in patients with myelofibrosis with myeloid metaplasia.

Neoangiogenesis is an integral component of bone marrow myeloproliferation in patients with myelofibrosis with myeloid metaplasia (MMM). As extramedullary haematopoiesis is a constitutive feature of MMM, we studied spleen neoangiogenesis by a computerized image analysis in MMM patients. Compared with five normal subjects, spleen CD34-staining capillary vascular density (CVD) was 2.1-3.03 times higher than the upper range of normal in six of the 15 (40%) MMM patients. CD8-staining sinusoidal vascular density (SVD) was constantly normal or lesser than normal and was inversely correlated with CVD (R = -0.53; P = 0.04). In MMM patients who did not receive cytoreductive or radiation therapy in the month before splenectomy (n = 9), the CVD was a significant determinant of spleen size (R = 0.88; P = 0.04). In MMM patients, the number of spleen CD34+ haematopoietic stem cells was increased from 1.2 to 98 times the upper limit of normal, and predicted the expansion of CVD (R = 0.57; P = 0.03). A population of cells expressing the CD34+/CD133+/VEGFR-2+ angiopoietic phenotype was present in the blood and spleen of five of seven patients. These results document that neoangiogenesis is an integral component of spleen re-localization of haematopoietic stem cells and suggest a cellular mechanism for spleen neoangiogenesis.

Adult↗

A comparison of low and high dose-rate radiation for recipient mice in spleen-colony studies.

Over the last 15 years, endogenous spleen-colony formation in our mice, following lethal irradiation, has increased to an unacceptable level. It has been found necessary, therefore, to introduce a new method of preparing recipient mice for spleen-colony studies. Irradiation with low dose-rate 60Cobalt gamma rays has been compared with high dose-rate linear accelerator electrons, and their effects on endogenous spleen colony formation compared with earlier X and gamma ray dose-response data. It was found that a large dose (13.5 Gy) of gamma rays results in fewer endogenous colonies than 8.5 Gy of electrons, yet because of its low dose rate (14.1 X 10(-3) Gy/min) it has a marked sparing of the intestinal tissue as measured by the intestinal microcolony technique. This in turn permits better survival and, therefore, a 'healthier' animal for spleen-colony work. Exogenous colony formation is also lower in the low dose-rate, gamma-irradiated recipients and this is shown to be due to a reduced spleen-seeding efficiency. It is concluded that very low dose-rate radiation is preferable for haemopoietic ablation, that a mouse colony requires constant monitoring for changes of endogenous spleen-colony formation and that the spleen-seeding efficiency of CFU-s depends on the irradiation technique used--there is no absolute value for a given strain of mouse.

Animals↗

Extramedullary haemopoiesis in fetal and adult human spleen: a quantitative immunohistological study.

Haemopoietic cells were assessed in spleens from normal adults, adults with splenic extramedullary haemopoiesis due to chronic myeloproliferative disorders and fetuses of 17-21 weeks' gestation. A variety of antigens expressed by developing granulocytes and erythrocytes were demonstrated immunohistochemically. The relative proportions of early and late precursor cells of these two lineages were quantified. There was no significant haemopoiesis in normal adult spleen, while there was abundant (predominantly granulocytic) haemopoiesis in patients with chronic myeloproliferative disorders. Fetal spleens contained numerous late erythroid precursors but few early erythroid or granulocytic cells. The relative numbers of early and late haemopoietic cells in adult chronic myeloproliferative disorders and fetal spleens showed statistically significant differences. Our findings indicate that haemopoiesis in the spleens of adult patients with these disorders differs fundamentally from that occurring in fetal life. They support the view that the human spleen does not have a significant role in fetal haemopoiesis, but that it filters circulating nucleated erythroid precursors and is permissive of their terminal differentiation only. Our results also favour the view that adult splenic haemopoiesis originates by displacement of precursor cells from the bone marrow rather than by activation of stem cells which have lain dormant in the spleen since fetal life.

Adult↗

The effect of various contexts of stress on the mouse spleen lymphocytes and macrophage co-stimulatory activity.

Mice stressed daily by brief cold water immersions for 1, 8 or 14 days showed changes in immune system function which were dependent on the number of mice per cage, frequency of stress exposures and total number of stress exposures. Changed percentages of spleen B and CD4, but not of CD8 cells were determined when the mice were stressed either once or twice daily. With CD4 cells, increased percentages were seen after stress once daily but a decreased percentage was seen after stress twice daily. Furthermore, the Concanavalin A-stimulated spleen cell mitogenesis was decreased after 1 day of stress in mice stressed once daily as opposed to after 8 and 14 days of stress in mice stressed twice daily. After 14 days of stress, the lipopolysaccharide stimulated mitogenesis was increased if the mice were stressed once daily but decreased if the mice were stressed twice daily. With two mice per cage, we observed a decreased spleen cell mitogenesis after 14 days of stress. With four mice per cage, the spleen cell mitogenesis was decreased after 8 and 14 days of stress. If spleen cell populations from mice stressed twice daily for 8 days were depleted of macrophages and CD4 or CD8 cells, the effect of stress on the mitogenesis was removed from the CD8 cells. Spleen cells of mice stressed for 14 days showed a decreased mitogenesis when depleted of adherent cells and reconstituted with adherent cells from control mice. Furthermore, the adherent cells from these mice had decreased ability to support mitogenesis of adherent cell-depleted spleen cells from control mice as well as a decreased IL-1 production.

Animals↗

Expression of mRNA encoding neurotrophins and neurotrophin receptors in rat thymus, spleen tissue and immunocompetent cells. Regulation of neurotrophin-4 mRNA expression by mitogens and leukotriene B4.

The expression of neurotrophin and neurotrophin receptor mRNAs was examined using RNase protection assays and Northern-blot analysis in rat thymus, spleen tissue and immunocompetent mononuclear cells purified from these two organs. Nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin-4 mRNAs were all expressed in thymus and spleen tissue although at different levels, while immunocompetent cells expressed neurotrophin-3 and neurotrophin-4 mRNAs. Thymus and spleen tissue expressed mRNAs encoding the low-affinity nerve-growth-factor receptor, the non-neuronal TrkA I receptor, the truncated (kinase deficient) and full-length TrkB, and the TrkC receptor. Low-affinity nerve-growth-factor receptor and non-neuronal TrkA I mRNAs were detected in both thymus and spleen immunocompetent cells. In addition, thymus cells expressed neuronal TrkA II mRNA and spleen cells expressed truncated TrkB mRNA. The expression of TrkA I and TrkA II mRNAs was enhanced in both thymus and spleen cells after cell culture. Enhanced levels of neurotrophin-4 mRNA were observed in spleen immunocompetent cells after adrenalectomy. Moreover, the expression of neurotrophin-4 mRNA was up-regulated after stimulation of immune cells with the mitogens concanavalin A or lipopolysaccharide or with the inflammatory mediator leukotriene B4. This suggests that neurotrophin-4 could be secreted by immunocompetent cells and may be involved in inflammatory processes.

Adrenalectomy↗

The influence of spleen size on liver regeneration after major hepatectomy in normal and early cirrhotic liver.

BACKGROUND/PURPOSE: The relationship between liver regeneration and spleen size after major hepatectomy in normal and cirrhotic liver was studied by single photon emission computed tomography (SPECT). MATERIALS AND METHODS: Twenty-six patients, 18 patients with normal liver and eight patients with cirrhotic liver, receiving major hepatectomy were included. Liver and spleen volumes were measured by SPECT before major hepatectomy, 6 months, 1 year and 2 years after operation. The correlation of liver and spleen volume during liver regeneration was analyzed. RESULTS: In both groups, the residual liver volume increased within the first year and decreased in the second year. No difference in regeneration ability was found. The spleen volume in cirrhotic liver was increased, with a trend similar to normal liver during the first year. In contrast, the increased spleen volume persisted up to the second year in cirrhotic patients. Age per year, the female sex, and body surface index had a positive correlation with increased percentage of liver volume. The spleen volume per 100 ml with time played a significantly negative role in increasing percentage of liver volume, confidence interval: -2.16 to -27.92, P=0.011. CONCLUSION: In early cirrhotic liver within normal functional limits, the liver still could regenerate as a normal liver after major hepatectomy in 1 year. Age, the female sex, and body surface index had positive correlation but the size of spleen volume played a negative role to regenerative liver volume.

Adult↗

Spleen size changes in children with homozygous beta-thalassaemia in relation to blood transfusion.

18 thalassaemic children, aged 3.5 to 13 years comprise our clinical material. In 14 of them clinically elicited spleen markings, haematocrit, blood platelet count and red cell morphology were studied daily for the whole period between transfusions. In 10 patients considerable changes in spleen size were noticed. According to out clinical observations the spleen size starts decreasing 1 to 3 d after blood transfusion up to the 10th posttransfusion day fluctuating thereafter to reach its maximum size again prior to the next blood transfusion. The decrease of spleen size was followed by an increase of haematocrit and blood platelet count and vice versa. 4 additional children were studied clinically only twice: prior to and 7 to 10 d after blood transfusion. A definite decrease of the spleen size following blood transfusion was observed. Spleen and liver 99mTc-sulfur colloid uptake was studied in 10 of the above children prior to and 7 to 10 d after blood transfusion. Statistically significant post-transfusion increase of the spleen uptake was demonstrated. Our findings suggest that (a) splenic size is relevant to blood volume sequestrated int this organ, (b) splenic radioactive uptake increases with its post-transfusion reduction in size.

Adolescent↗

The spleen in Felty's syndrome: a histological, morphometrical, and immunohistochemical study.

A histological study employing morphometrical and immunohistochemical methods was performed in 3 spleens removed because of Felty's syndrome (FS). A comparison was made with control spleens and with spleens removed from patients with idiopathic thrombocytopenic purpura (ITP) or autoimmune hemolytic anemia (AIHA). In FS, the spleen is enlarged, mainly due to expansion of the red pulp. The sinuses are enlarged, too, and contain many macrophages. 2 of our specimens showed many hyperplastic germinal centers; the 3rd contained no germinal centers. Only in the former cases did splenectomy lead to an increase in the number of circulating granulocytes. Immunohistologically, FS spleens differed from the control, the ITP, and the AIHA spleens. The results have provided further evidence indicating that the pathogenesis of granulocytopenia in FS differs from that of autoimmune hematocytopenias, and have given rise to the hypothesis that, in FS, the spleen is the site of interaction between immune complexes and granulocytes.

Anemia, Hemolytic, Autoimmune↗

Inhibitory and stimulatory effect of spleen cells from tumour bearing animals on the growth of syngeneic tumour cells.

When spleen cells from C3H mice inoculated with a primary spontaneously arisen C3H mammary carcinoma were added to tumour target cells of the same type in vitro, both an inhibitory and a stimulatory effect on target cell growth were seen, when compared with the effect of adding normal syngeneic spleen cells. The inhibitory effect was seen regularly when high concentrations of spleen cells were added, while there was a stimulatory effect when low concentrations were added to the tumour target cells. When transferring spleen cells from tumour bearing mice together with a tumour inoculum to groups of normal syngeneic recipients, the resultant tumour growth was enhanced, as compared with recipients given tumour plus normal spleen cells and those given tumour cells only. It was found that the spleen cells which caused the greastest enhancement in vitro caused the greatest inhibition in vitro. This relationship could be explained by assuming the occurrence in spleens of tumour bearers of a population of reactive cells which when added in high concentrations to tumour target cells in vitro cause inhibition, while they cause stimulation of tumour growth in vivo because of being transferred to recipients in relatively low concentrations.

Animals↗

Component(s) of Sendai virus that can induce interferon in mouse spleen cells.

To identify the active component of Sendai virus that induces interferon in mouse spleen cells, infectious and noninfectious viruses, envelope particles derived from them, and isolated hemagglutinin-neuraminidase (HN) glycoproteins were examined for interferon induction. The interaction between membranous structures containing Sendai virus HN glycoprotein and the receptors on the cell surface was shown to be sufficient for interferon induction in mouse spleen cells, suggesting that the actual inducer of interferon in mouse spleen cells is the HN glycoprotein of Sendai virus. When mouse spleen cells were stimulated in vitro with Sendai virus grown in eggs or LLC-MK2 cells or with membranous structures containing glycoproteins obtained from these viruses, interferon could be detected in the culture fluid. Furthermore, isolated HN glycoprotein per se could induce interferon in the cells. A linear correlation was found between the titer of interferon induced and the hemagglutinating activity of the membranous structure containing the HN glycoprotein. It was concluded from these findings that HN glycoprotein was the active component of Sendai virus responsible for interferon induction in mouse spleen cells and that viral RNA and F glycoprotein were not required. The results also showed that the interaction between HN glycoprotein and receptors on the cell surface triggered production of type I interferon (IFN-alpha and IFN-beta). Although when Sendai virus was incubated at 56 degrees C for 5 min it lost its hemolytic and hemagglutinating activities, it induced a considerable amount of interferon in the culture fluid of mouse spleen cells. The interferon-inducing ability of heat-inactivated virus could be absorbed with mouse spleen cells but not with sheep erythrocytes or mouse erythrocytes, indicating that the inactivated virus retained ability to bind to mouse lymphoid cells.

Animals↗

Differential requirements for an intact spleen in induction and expression of B-cell-dependent immunity to Plasmodium chabaudi AS.

The requirement for an architecturally intact spleen in the afferent and efferent arms of immunity to the murine malaria parasite Plasmodium chabaudi AS was analyzed. C57BL/6 mice with intact spleens develop a single, patent parasitemia and resolve the infection. In contrast, surgically splenectomized mice experience persistent waves of patent parasitemia interrupted briefly by periods of parasitologic crises. Transfer of spleen cells from immune donors, but not transfer of spleen cells from normal mice, into splenectomized mice enabled the recipients to resolve the infection similar to mice with intact spleens. B-cell depletion, but not T-cell depletion, of spleen cells prior to transfer abrogated the ability of splenectomized recipients to resolve the infection. Compared with mice with intact spleens, splenectomized mice exhibited a delayed antibody response whereas all groups of immune cell recipients had an accelerated antibody response. Nevertheless, splenectomized mice and recipients of B-cell-depleted cells failed to resolve infections, despite the development of high-titer antibodies late during the course of infection. Analysis of immunoglobulin G isotype responses showed a lower representation of immunoglobulin G2a in mice which failed to resolve infections. The latter mice had characteristic histopathologic changes in the liver. These observations indicate a unique role of the splenic microenvironment for the induction and development of an effective B-cell-dependent response against malarial parasites.

Animals↗

Identification of a spleen focus-forming virus in erythroleukemic mice infected with a wild-mouse ecotropic murine leukemia virus.

An NFS/N mouse inoculated at birth with an ecotropic murine leukemia virus (MuLV) obtained from wild mice (Cas-Br-M MuLV) developed a lymphoma after 18 weeks. An extract prepared from the lymphomatous spleen was inoculated into newborn NFS/N mice, and these mice developed erythroleukemia within 9 weeks. Spleens from the erythroleukemic mice contained ecotropic and mink cell focus-inducing (MCF) MuLVs; however, when these viruses were biologically cloned and reinoculated into newborn NFS/N mice, no erythroleukemia was induced. In contrast, cell-free extracts prepared from the erythroleukemic spleens induced erythroleukemia within 5 weeks. Analysis of cell-free extracts prepared from the erythroleukemic spleens showed that they contained a viral species that induced splenomegaly and spleen focus formation in adult mice, with susceptibility controlled by alleles at the Fv-2 locus. The spleen focus-forming virus coded for a 50,000-dalton protein precipitated by antibodies specific to MCF virus gp70. RNA blot hybridization studies showed the genomic viral RNA to be 7.5 kilobases and to hybridize strongly to a xenotropic or MCF envelope-specific probe but not to hybridize with an ecotropic virus envelope-specific probe. The virus described here appears to be the fourth independent isolate of a MuLV with spleen focus-forming activity.

Animals↗

Ultrasound assessment of spleen size in collegiate athletes.

OBJECTIVES: To determine normal spleen dimensions in a healthy collegiate athletic population. METHODS: 631 Division I collegiate athletes from one university participated in the study. During pre-participation examinations, demographic data collected were collected from volunteer athletes including sex, race, measurement of height and weight, and age. Subjects also completed a medical history form to determine any history of mononucleosis infection, platelet disorder, sickle cell disease (or trait), thalassaemia, or recent viral symptoms. Subjects then underwent a limited abdominal ultrasound examination, where splenic length and width were recorded. RESULTS: Mean (SD) splenic length was 10.65 (1.55) cm and width, 5.16 (1.21) cm. Men had larger spleens than women (p<0.001). White subjects had larger spleens than African-American subjects (p<0.001). A previous history of infectious mononucleosis or the presence of recent cold symptoms had no significant affect on spleen size. In more than 7% of athletes, baseline spleen size met current criteria for splenomegaly. CONCLUSIONS: There is a wide range of normal spleen size among collegiate athletes. Average spleen size was larger in men and white athletes than in women and black athletes. A single ultrasound examination for determination of splenomegaly is of limited value in this population.

Adult↗

Validation and standardization of Kveim test suspensions prepared from two human sarcoid spleens.

Single lots of a Chase-Siltzbach type I Kveim test material from each of two sarcoid spleens and designated lot 5 of spleen K12 and lot 1 of spleen K13 have been validated alongside a single lot (lot 10) of a 'standard' suspension provided by Dr L. E. Siltzbach and prepared identically from the spleen of patient J (SPLEEN J) in New York. Additionally, a half-dilution of lot 5, K12, was included in this comparison. The reactivity of each suspension was assessed among patients with active and inactive sarcoidosis. The selectivity of each suspension for sarcoidosis was assessed similarly by comparison with results in patients with active and quiescent pulmonary parenchymal tuberculosis and in healthy subjects. All patients were closely matched and two Kveim tests were made in each subject according to a prearranged statistical design. The reactivity of the K12, K12 1/2 dilution, and K13 suspensions among patients with active and inactive sarcoidosis was closely similar to that with the 'standard' S10 suspension and in accordance with the expected proportions of reactions in patients at different stages of sarcoidosis. The K12, K13, and 'standard' S10 suspensions yielded a negligible proportion of positive reactions among patients with active and quiescent pulmonary tuberculosis and among healthy subjects: thus, as judged by these tests each suspension showed a high degree of selectivity for sarcoidosis. The results of this validation study are discussed in relation to the results of other studies in which lots 5 and 14 of K12 and early and late batches of a suspension prepared from another sarcoid spleen at the Commonwealth Serum Laboratories designated CSL and provided by Dr T.H. Hurley in Melbourne were employed. Using lot 5 of K12 positive reactions were found in an appreciable proportion of patients with Crohn's disease, ulcerative colitis, and tuberculous lymphadenitis. A closely similar rate of positive reactions was encountered among patients with Crohn's disease following tests with batch 0025 of CSL suspension and with another lot (lot 14) derived from spleen K12. A close concordance of results was obtained with lot 5(K12) and with batch 0042 CSL among patients with ulcerative colitis, but at a lower rate of reactivity. We conclude that positive reactions also occur in some diseases other than sarcoidosis and consider that the difficulties in determining the criteria for an acceptable test suspension become increasingly apparent as additional Kveim tests are made with one particular lot and with seqential lots of material from a 'validated' tissue source.

Adult↗

Ontogeny of 2-[125I]iodomelatonin binding sites in the chicken (Gallus domesticus) kidney and spleen.

To understand the possible role of melatonin receptors in the development of renal and immune functions, age-related variations of 2-[125I]iodomelatonin binding sites in the chicken kidney and spleen were investigated by radioreceptor assay. Chickens at embryonic day 20, as well as 2 days, 9 days, 2 weeks, 6 weeks, 12 weeks, and 16 weeks after hatching, were kept under a 12 h light:12 h dark photoperiod and killed at the middle of the light period. Binding sites for 2-[125I]iodomelatonin in membrane preparations of the chicken kidney and spleen were present on embryonic day 20. The maximum binding densities (Bmax) in the kidney increased to a peak between 9 days and 2 weeks of age, then progressively decreased. Bmax values of 2-[125I]iodomelatonin binding sites in the chicken spleen were lower than in the kidney. The peak density in the chicken spleen was recorded at day 2 after hatching and decreased significantly after 6 weeks of age. There were no significant differences in binding affinities (Kd) in kidney and spleen of chicken in the different age groups studied. The unity of Hill coefficients of 2-[125I]iodomelatonin binding sites of the chicken kidney and spleen in all age groups tested suggested that only a single class of binding sites was present in these tissues during development. It is proposed that the developmental changes in 2-[125I]iodomelatonin binding sites in the chicken kidney and spleen may be pertinent to the development of diurnal rhythms of kidney functions and the post-pubertal decline in immune functions of the chicken.

Age Factors↗

Difference between liver and spleen CT numbers in the normal adult: its usefulness in predicting the presence of diffuse liver disease.

A constant relationship was found between the mean CT numbers of the liver and spleen in 100 normal adults. This relationship was characterized by a mean CT number consistently higher for the liver (24.9 +/- 4.6) than for the spleen (21.1 +/- 4.1). The range for liver CT numbers was 16.7-37.2, and for the spleen it was 14.9-34.3. The mean liver-spleen CT number difference for all subjects was 3.8 +/- 2.1 (p < 0.001); in every instance, the livers exhibiting the high mean CT numbers were in subjects with high mean spleen CT numbers, with the same concordance for low mean CT numbers. This relationship between liver and spleen may be useful in the clinical setting in which a normal liver with low CT numbers must be differentiated from one in which the CT number is low because of fatty infiltration; the fatty liver will exhibit a lower mean CT number than the spleen.

Adult↗