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PubMed2002

Suppressed proliferative response of spleen T cells from metallothionein null mice.

To investigate the role of metal-binding protein, metallothionein (MT), in lymphocyte activation, the mitogen-induced proliferation of freshly isolated spleen cells was compared among MT-I, II null, and control 129/Sv mice. Spleen cells from MT null mice exhibited a markedly reduced proliferation compared with control cells when stimulated by concanavalin A or anti-CD3(epsilon) mAb, but not by lipopolysaccharide, indicating that only the response of T cells to mitogens was suppressed in MT null mice. Flow cytometric analysis of unstimulated spleen cells demonstrated no significant difference in the relative percentages of either B220+ and CD3+ cells or CD4+ and CD8+ cells between the two strains of mice. The production of interleukin (IL)-2 by MT null spleen cells after the stimulation by anti-CD3(epsilon) mAb was lower than that of control spleen cells, especially within 24 hr after the stimulation. The addition of IL-2 recovered the proliferation of MT null spleen cells to the control level. The reduced proliferative response to mitogenic stimulation of MT null T cells was confirmed by using purified splenic T cells. These results suggest that the MT expressed at basal level in the splenocytes plays an important role in T cell mitogen-induced proliferative response, probably by positively regulating the production of IL-2.

Animals↗
PubMed1983

The relationship between human spleen and blood erythroid burstforming units (BFU-E).

The influence of splenectomy on erythroid burst colony formation by peripheral blood mononuclear cells from 10 patients (four with hereditary spherocytosis, two with beta-thalassaemia major, two with Hodgkin's disease and two with idiopathic thrombocytopenic purpura) was studied. In every instance splenectomy was followed by a lowering of blood BFU-E. The post-splenectomy levels ranged from 0 to 30% of the preoperative levels. Mononuclear cells from the spleens of eight patients were cultured and found to contain numerous BFU-E. The total quantity of BFU-E in the whole blood and in the spleen of the patients was generally of the same order of magnitude. The number of splenic BFU-E did not correlate with spleen size. Splenic BFU-E differed from peripheral blood BFU-E in that they were more sensitive to erythropoietin (Ep) and in that they failed to respond to burst promoting activity (BPA) produced by preincubating the spleen mononuclear cells with phytohaemagglutinin M (PHA). In contrast, media conditioned by PHA-treated spleen cells contained BPA active on peripheral blood BFU-E from normal individuals. These data suggest that the spleen may have an influence on the numbers and functional properties of BFU-E.

Adolescent↗
PubMed2005

A defective Th1 response of the spleen in the initial phase may explain why splenectomy helps prevent a Listeria infection.

Listeria monocytogenes (Listeria) are known to grow and proliferate in the liver while a splenectomy induces host resistance against a Listeria infection despite the fact that a splenectomy inhibits the Th1 response. Therefore, the mechanism by which a splenectomy helps to prevent the growth of Listeria still remains to be elucidated. After an i.v. challenge of Listeria (1 x 10(6) CFU) in C57BL/6 mice, Listeria rapidly increased in the spleen but not in the liver until 48 h. However, after this initial phase, Listeria remarkably grew in the liver. In contrast, when the mice received a splenectomy beforehand, no remarkable growth of Listeria in the liver was observed after Listeria challenge despite the fact that serum IFN-gamma and IL-12 levels at 24 h after Listeria challenge were significantly lower than those in the sham mice. However, the liver leucocytes from mice by 6 h after infection produced a substantial amount of IFN-gamma while spleen MNC did not, whereas spleen leucocytes at 24 h after Listeria challenge did. Consistently, the IFN-gamma and IL-12 levels in the tissue homogenates of the spleen were significantly lower than in those of the liver until 6 h after infection. This defective spleen Th1 response in the early phase of Listeria infection was corrected by an IL-18 i.p. injection just after the Listeria challenge. Our findings suggest that Listeria exploit the defective Th1 environment of the spleen in the initial phase and afterwards overcome the host defense mechanism of the liver.

Animals↗
PubMed1979

Phytohaemagglutinin responsiveness of non-adherent nude spleen cells.

Non-adherent spleen cells from athymic nude mice showed incorporation of tritiated thymidine (3H-TdR) at a level comparable to that of non-adherent cells of normal mice when stimulated with the T-cell mitogen phytohaemagglutinin (PHA). The optimal dose of PHA was 50 microliter/ml for nude cells, a concentration that does not stimulate normal cells. In comparison, 2.5 microliter/ml PHA was optimal for cells of normal mice. Anti-theta serum plus complement treatment of the non-adherent nude spleen cells reduced 3H-TdR incorporation by approximately 50%, suggesting that some of the responding cells carried the theta antigen. Direct immunofluorescence showed that the non-adherent nude spleen cells contained 6-9% theta-positive cells. In comparison, more than 80% of the PHA-induced nude blast cells were theta-positive. PHA-induced DNA synthesis of normal mouse spleen cells was inhibited by adherent nude spleen cells. No theta-antigen or surface immunoglobulin could be demonstrated on these inhibitory cells, suggesting that they belong to the macrophage system of the nude mouse spleen.

Animals↗
PubMed1971

Release of noradrenaline and dopamine by nerve stimulation in the cat spleen perfused with 3 H-dopamine.

1. Recovery of (3)H-dopamine and (3)H-L-dopa infused intra-arterially at a constant rate of 20 ng/min into the cat spleen perfused with Krebs bicarbonate solution was 52.6+/-3.8% and 90.5+/-3.1% respectively. Recovery of (3)H-dopamine in spleens treated with alpha-methyl-p-tyrosine was 67.7+/-6.7% and was not significantly different from untreated spleens.2. Release of (3)H-dopamine by nerve stimulation after an infusion of (3)H-dopamine resembled release of endogenous noradrenaline. Release of (3)H-L-dopa and (3)H-L-tyrosine after their infusion did not occur in any consistent manner by nerve stimulation.3. Preferential release of (3)H-noradrenaline formed from (3)H-dopamine was not observed during continuous nerve stimulation. Specific activity of released (3)H-noradrenaline remained constant during any single stimulation period with or without (3)H-dopamine infusion. Treating the cats with alpha-methyl-p-tyrosine did not change the time course of (3)H-noradrenaline release.4. Output of noradrenaline expressed as a percentage of the first minute output in both normal and alpha-methyl-p-tyrosine treated spleens was not significantly different at various times during continuous nerve stimulation.5. Specific activity of released noradrenaline formed from (3)H-dopamine was always greater than the specific activity of the spleen in normal spleens and spleens treated with alpha-methyl-p-tyrosine.6. It is concluded that newly synthesized or infused noradrenaline initially mixes with a more rapidly turning pool and only slowly with the entire tissue store. During continuous nerve stimulation there is no further preferential release of newly synthesized noradrenaline. Released noradrenaline truly represents the state of the releasable pool and will vary with the latter.

Animals↗
PubMed2004

Expression of Fas and Fas ligand on spleen T cells of experimental animals after unmodified or leukoreduced allogeneic blood transfusions.

BACKGROUND: The clonal deletion seen in recipients of allogeneic blood transfusion (ABT) refers to the removal of lymphocytes that promote the clearance of transfused alloantigens. Interactions between Fas (CD95) and FasL (CD95L) are involved in the clonal deletion of T cells and in the down regulation of the cytotoxic T-cell activity. STUDY DESIGN AND METHODS: The expression of CD95/95 L on spleen T cells of C57Bl/6 mice infused with unmodified ABT, prestorage leukoreduced ABT (LR-ABT), or saline was investigated by flow cytometry. The numbers of apoptotic spleen cells were evaluated after transfusion using the acridine orange and ethidium bromide uptake technique. RESULTS: Compared with untransfused animals, mice transfused with ABT showed higher expression of CD95 (MFI = 94.4 +/- 8.6 vs. 73.1 +/- 7.9, p = 0.02) and CD95L (23.5 +/- 6.9 vs. 8.1 +/- 2.0, p = 0.008) on CD4+ spleen cells. Expression of CD95 (92.2 +/- 7.5 vs. 64.9 +/- 7.5, p = 0.007) and CD95L (17.7 +/- 3.6 vs. 8.2 +/- 2.2, p = 0.02) was also increased on CD8+ cells of these animals. CD8+ spleen cells from mice transfused with ABT showed higher expression of CD95 (92.2 +/- 7.5 vs. 76.9 +/- 4.0, p = 0.03) and CD95L (17.7 +/- 3.6 vs. 8.3 +/- 1.5, p = 0.03) than cells from mice transfused with LR-ABT. The number of apoptotic spleen cells from mice transfused with ABT was greater than that from mice infused with LR-ABT (10.9 +/- 1.3 vs. 6.6 +/- 1.8, p = 0.01) or saline (10.9 +/- 1.3 vs. 6.5 +/- 0.7, p = 0.001). CONCLUSIONS: The data suggest that ABT up-regulates the expression of Fas/FasL on spleen T cells of mice and may promote their apoptosis. These ABT-associated immunologic alterations can be partially prevented by the leukoreduction of the transfused blood.

Animals↗
PubMed2002

Evaluation of cytokine gene expression in porcine spleen cells, peripheral blood mononuclear cells, and alveolar macrophages by competitive RT-PCR.

Cytokines act as an important regulator of immune responses. Since cytokine expression levels are generally very low, more accurate and reliable methods of measuring their expression are needed. In this study, a modified competitive reverse transcription-polymerase chain reaction assay was developed to determine the expression levels and patterns of porcine IFN-gamma, IL-2, IL-4, IL-10, IL-12 p 35, and IL-12 p40 in spleen cells, peripheral blood mononuclear cells (PBMC), and alveolar macrophages that were stimulated for 4 h by lipopolysaccharide or phytohemagglutinin. Of these cytokines, the expression level of IFN-gamma was the highest in all examined cells. Constitutive expression of IL-2 and IL-4 was demonstrated in spleen cells and PBMC stimulated with phytohemagglutinin. However, their expression extent was not determinable or extremely low in the lipopolysaccharide-stimulated spleen cells and alveolar macrophages. Moderately high IL-10 expression was observed in all examined cells. IL-12 p 35 expression in alveolar macrophages was always higher than in spleen cells and PBMC. IL-12 p40 expression in alveolar macrophages was higher than in PBMC, but was lower than in spleen cells. In spleen cells, the expression of IL-12 p40 was higher than that of IL-12 p 35. In alveolar macrophages and PBMC, however, IL-12 p 35 showed a higher expression than IL-12 p40. These results indicate that each cytokine has its own characteristic expression profile in different immune cells.

Animals↗
PubMed1981

Detection of splenosis and ectopic spleens with 99mTc-labelled heat damaged autologous erythrocytes in 90 splenectomized patients.

Splenosis or ectopic spleens were detected in 22 of 45 patients splenectomized after either abdominal trauma or accidental lesions of the spleen during operation. The incidence of ectopic spleen tissue in various groups of splenectomized patients has been investigated by a sensitive scanning method employing reinjection of 99mTc-labelled heat damaged autologous erythrocytes. In comparison 7 cases were found among 45 patients who underwent splenectomy for haematological reasons. The time span between the operation and a positive scan varied between 3 months and 11 years. None of the patients in the haematological group with reoccurrence of spleen tissue presented any signs of relapse of their primary disorder. The only patient with overwhelming infection was a girl in whom splenectomy was performed for hereditary spherocytosis. She recovered from the sepsis and her scan was negative. It is concluded that recurrence of spleen tissue is frequent after traumatic lesions of the spleen but rare after selective splenectomy for haematological reasons. This may account for the lesser tendency to overwhelming sepsis after post-traumatic splenectomy.

Adolescent↗
PubMed1983

Influence of the spleen on the distribution of blood neutrophils. Quantitative studies in the rat.

The influence of the spleen on the distribution of blood neutrophils was studied in rats with varying spleen sizes following transfusion of isologous 3H-dT-labelled neutrophils. The weight of the spleen correlated with the splenic neutrophil pool (r = 0.87, P less than 0.01). Alterations in spleen size did not significantly change the total blood neutrophil pool, but with increasing splenomegaly circulating and marginal neutrophils were shifted into the splenic pool. With massive splenomegaly, up to 50% of the total blood neutrophils were trapped in the spleen. These findings suggest splenic pooling of neutrophils and a shift of circulating and marginal neutrophils into the spleen proportionate to the splenic tissue present.

Animals↗
PubMed1999

The red cell mass, plasma erythropoietin and spleen size in apparent polycythaemia.

It has been shown previously that measurement of the spleen size and plasma erythropoietin (EPO) concentration are valuable adjuncts in the diagnostic work-up of patients with polycythaemia vera. The aim of the present work was to evaluate their value in the assessment of apparent polycythaemia (AP). Therefore, over a 24-month period we routinely performed bone marrow biopsies, measurement of red cell mass (RCM) and plasma volume (PV), spleen size determination by gamma camera scintigraphy and determination of the plasma EPO concentration in consecutive patients referred to us because of elevated values for packed cell volume (>0.48 in females and >0.51 in males). After having excluded patients with clonal and secondary polycythaemias we were left with 38 patients (27 males and 11 females) with AP. In all of them the measured RCM was within normal range, i.e. <36 ml/kg for males and <32 ml/kg for females. The subjects were characterized by moderate increase in RCM and a concomitant moderate decrease in PV. Thus, as an average the measured RCM exceeded the predicted values by 14% in males and by 12% in females; conversely, as compared to the predicted values the average measured value for PV was reduced by 17% in males and by 8% in females. The average RCM for males was 29+/-3 ml/kg; the corresponding figure for females was 23+/-4 ml/kg. It was shown that 86% of the subjects had plasma EPO concentrations within the control range; the remaining had values slightly above or below the control range. The mean posterior spleen scan area was 57+/-16 cm2 and mean left lateral area 57+/-17 cm2; the reference value for spleen scan area (for both projections) is 57+/-12 cm2. Of the patients 35/38 (92%) had a spleen scan area within the mean+2SD for controls and 38 subjects (100%) had values within the mean+3SD. It is concluded that measurement of plasma EPO and a careful assessment of the spleen size should always be considered in the evaluation of patients with elevated values for venous packed cell volume.

Adult↗
PubMed1976

Release of noradrenaline from the cat spleen by nerve stimulation and potassium.

1. Release of noradrenaline from the perfused cat spleen, or from isolated spleen slices, in response to prolonged nerve stimulation or maintained depolarization by potassium was measured. 2. Prolonged stimulation of the splenic nerves at 2, 10 and 30 Hz for 10 min evoked release, which was maximum during the first 2 min, and then declined during the remaining period of stimulation. When noradrenaline release was induced by high potassium from the perfused spleen or from isolated slices, it followed a similar time course to nerve stimulation. Similar results were obtained from phenoxybenzamine-treated spleens, using both modes of stimulation. 3. Stimulation of the splenic nerves in calcium-free Krebs solution did not release noradrenaline. If calcium was introduced at a later stage during stimulation, the release was markedly diminished. In phenoxybenzamine- or phentolamine-treated spleens, stimulation of the nerves in the presence of calcium evoked a secretory response which was comparable to the one produced by introduction of calcium after a few minutes of nerve stimulation. 4. Simultaneous application of calcium plus high potassium always produced a much greater secretion of noradrenaline than application of calcium after a few minutes of potassium depolarization. Release of noradrenaline by potassium from phenoxybenzamine-treated spleens was also much greater if calcium and potassium were added simultaneously than addition of calcium after a few minutes of potassium depolarization. 5. In the presence of maintained depolarization by potasssium, tyramine was effective in causing release of noradrenaline.

Animals↗
PubMed1979

Suppression of in vitro antibody response by spleen cells of mice infected with Friend-associated lymphatic leukemia virus.

The ability of spleen cells of mice infected with oncornaviruses to depress the in vitro antibody responsiveness of normal lymphoid cells was exploited in an attempt to clarify the role played by the lymphatic leukemia virus (LLV) component in the immunodepressive properties of the Friend leukemia complex. Spleen cells of mice infected with LLV or, for comparison, with the entire complex were added to cultures of sheep erythrocyte-primed uninfected spleen cells, and the antibody-forming cells produced by the latter, after antigen restimulation, were assayed. The addition within 2 days from culture initiation of low numbers of cells infected with either virus preparation suppressed all stages of the response affecting the production of both immunoglobulin M and immunoglobulin G antibody. The activity of infected cells resisted doses of ultraviolet radiation which inhibit cell multiplication but was abolished by disrupting the cells and was prevented by the presence of anti-LLV antibodies. The LLV-infected spleen cells responsible for suppression were not removed by treatments which selectively remove or kill macrophages and exhibited surface properties of B lymphocytes. These results were interpreted as indicating that the effect is due to virus (or viral products) released by B cells. The suppressing cells in the spleens of mice in the early days of Friend leukemia complex infection presented superimposable properties, supporting the concept that their activity is also due to the LLV they release in large quantities. However, in later stages of infection, the spleens of Friend leukemia complex-infected mice also contained non-B-suppressing cells possibly derived from the proliferation of nonlymphoid LLV-producing cells caused by the neoplastic process.

Animals↗
PubMed1981

Recovery of mice from herpes simplex virus type 2 hepatitis: adoptive transfer of recovery with immune spleen cells.

Young BALB/c mice inoculated intraperitoneally with herpes simplex virus type 2 develop focal necrotizing hepatitis. After infection, the livers of these mice show increasing virus titers, which reach a maximum on day 3 after infection; this is followed by a dramatic decrease in the amount of virus recovered on days 4 and 5. This decrease in virus content is accompanied by a progressive infiltration of the lesions with mononuclear leukocytes and an apparent resolution of the lesions. Adoptive transfer of immune spleen cells from mice infected 6 days earlier accelerated this process. When 50 x 10(6) to 100 x 10(6) immune spleen cells were transferred 24 h after infection, the inflammatory response and the clearance of virus from the livers were advanced by almost 2 days. As few as 12 x 10(6) immune spleen cells accelerated the healing process, whereas fewer immune cells, disrupted immune cells, or normal spleen cells did not have an effect. The protection conferred by herpes simplex virus type 2-sensitized immune spleen cells was specific since mouse cytomegalovirus- or vaccinia virus-sensitized immune spleen cells had no effect on the course of infection with herpes simplex virus type 2, whereas some cross-reactivity was observed between herpes simplex virus types 1 and 2. This model seems to be suitable for examining the immunological mechanisms that are active during recovery from visceral herpes simplex virus infections.

Animals↗
PubMed1991

Testosterone-induced abrogation of self-healing of Plasmodium chabaudi malaria in B10 mice: mediation by spleen cells.

This study investigates the suppressive effect of testosterone (Te) on the self-healing of Plasmodium chabaudi malaria in female mice of the strain C57BL/10, and, in particular, the possible role of spleen cells in mediating this Te effect. Our data show the following. (i) About 80% of B10 mice infected with 10(6) P. chabaudi-infected erythrocytes are capable of self-healing the infections. This capability is progressively impaired and finally abrogated after pretreating the B10 mice with Te for 3 weeks. (ii) The spleen is Te responsive. This becomes evident in a reduction of total spleen cells from 1.05 x 10(8) to 0.54 x 10(8) on average after Te treatment for 3 weeks. Moreover, Te treatment causes an increase in the relative proportion of CD8+ cells by about 4% and a decrease of Ig+ cells by about 4.5%, as revealed by flow cytometry. (iii) Spleen cells mediate the suppressive Te effect as revealed by adoptive transfer experiments. The percentage of self-healing mice dramatically decreases to about 8% when they receive, just prior to infection, nucleated spleen cells isolated from mice treated with Te for 3 weeks. This suppressive effect can be transferred by T cells in particular but also by non-T cells, though to a lesser extent. (iv) The adoptively transferred cells mediate their suppressive effect on self-healing only if the recipient mice receive Te during infection. Our data suggest that spleen cells become functionally changed by the Te treatment for 3 weeks. Particularly T cells, but also non-T cells, gain P. chabaudi-specific suppressive activities, and the cells require a Te-induced factor(s) to mediate these activities.

Animals↗
PubMed1979

Persistence of infectious Friend virus in spleens of mice after spontaneous recovery from virus-induced erythroleukemia.

Persistent infectious virus was detected in the majority of spleens of (C57BL/10 X A.BY)F1 mice after spontaneous recovery from Friend virus-induced erythroleukeima. The Friend murine leukemia helper virus (F-MuLV) was detected in titers up to 3 X 10(5) PFU/g of spleen. The defective spleen focus-forming virus (SFFV) was present in much lower titers and could be detected in cell-free spleen homogenates only after amplification of virus titer by growth of virus in vitro on SC1 cells. The incidence of cells producing F-MuLV alone in spleens after recovery from leukemia was 0.003 to 0.3%, and the incidence of cells producing both F-MuLV and SFFV was less than 0.0001 to 0.01%. In most recovered mouse spleens there appeared to be a selective reduction of SFFV relative to F-MuLV.

Animals↗
PubMed2006

Resistance of neonatal mice to scrapie is associated with inefficient infection of the immature spleen.

Previous studies demonstrated that neonatal mice up to about a week old are less susceptible than adult mice to infection by intraperitoneal inoculation with mouse-passaged scrapie. In peripherally inoculated adult mice, scrapie replicates in lymphoid tissues such as the spleen before invading the central nervous system. Here, we investigated scrapie susceptibility in neonatal mice in more detail, concentrating on spleen involvement. First, we demonstrated that neonatal mice are about 10 times less susceptible than adults to intraperitoneal scrapie inoculation. Then we injected mice intraperitoneally with a scrapie dose that produced disease in all mice inoculated at 10 days or older but in only about a third of neonatally inoculated mice. In this experiment, spleens collected 70 days after scrapie injection of mice 10 days old or older almost all contained pathological prion protein, PrPSc, and those that were bioassayed all contained high infectivity levels. In contrast, at this early stage, only two of six spleens from neonatally inoculated mice had detectable, low infectivity levels; no PrPSc was detected, even in the two spleens. Therefore, neonatal mice have an impaired ability to replicate scrapie in their spleens, suggesting that replication sites are absent or sparse at birth but mature within 10 days. The increase in susceptibility with age correlated with the first immunocytochemical detection of the normal cellular form of prion protein, PrPc, on maturing follicular dendritic cell networks. As lymphoid tissues are more mature at birth in sheep, cattle, and humans than in mice, our results suggest that in utero infection with scrapie-like agents is theoretically possible in these species.

Animals↗
PubMed1990

Abnormalities of the spleen in relation to congenital malformations of the heart: a survey of necropsy findings in children.

A series of 1042 reports of necropsies on children dying at Children's Hospital of Pittsburgh was reviewed. In each case, note was taken of the status of the spleen, the lobation of the lungs, the arrangement of the bronchi, the morphology of the atrial appendages, and the presence of any congenital malformations of the heart and great vessels and of any malformations of the abdominal organs. There was isomerism of the left atrial appendages in eight (0.77%), 13 (1.25%) showed isomerism of the right appendages, and seven (0.67%) had multiple spleens without having isomerism of the atrial appendages. Unexpectedly, a normal spleen was found in one patient with isomerism of the right appendages and also in a patient with isomerism of the left appendages. In one patient with isomeric left atrial appendages there was no spleen. The review showed that the morphology of the atrial appendages, and hence the arrangement of the atria, is not accurately predicted by the type of spleen. The arrangement of the atrial appendages is the most reliable guide to the recognised combinations of congenital cardiac malformations previously described as "splenic syndromes". Because there is no certain way of predicting all the malformations in patients with complex congenital heart disease, it is advisable to record separately for each patient the details of lobation of the lungs, the bronchial and atrial arrangement, anomalies of the heart and great vessels, the type of spleen, and any abnormal arrangement of the abdominal organs.

Abnormalities, Multiple↗
PubMed2004

Nitric oxide induces apoptosis in spleen lymphocytes from MRL/lpr mice.

BACKGROUND: MRL/MpJ-Tnfrsf6lpr(MRL/lpr) mice, a murine model of systemic lupus erythematosus (SLE), have defective expression of Fas, substantially reducing signaling for apoptosis via this mechanism. However, it is known that MRL/lpr mice have increased spontaneous apoptosis of leukocytes. These conflicting observations have stimulated interest in apoptosis in this SLE model. MRL/lpr mice overproduce nitric oxide (NO) as autoimmune disease progresses. In vitro administration of NO may induce or decrease apoptosis depending on the cell type. Therefore, we hypothesized that NO induces MRL/lpr spleen lymphocyte apoptosis independent of Fas receptor engagement. METHODS: Percentages of apoptotic spleen lymphocytes from MRL/lpr and BALB/cJ mice were determined ex vivo after in vivo treatment with NG-monomethyl-L-arginine (NMMA), a nitric oxide synthase (NOS) inhibitor. After culture in varying concentrations of a slow-acting NO donor, the following were determined in spleen lymphocytes: (1) levels of apoptosis, (2) the effect of phorbol myristate acid (PMA) on levels of NO-induced apoptosis, and (3) protein kinase C (PKC) activity. RESULTS: Spleen lymphocytes from MRL/lpr mice with active disease had increased levels of ex vivo apoptosis when compared with BALB/cJ controls. This increase was reduced by pharmacologic inhibition of NOS in MRL/lpr but not in BALB/cJ mice. Exogenous administration of NO in vitro reduced PKC activity and induced apoptosis in MRL/lpr spleen lymphocytes, an effect that could be reduced via coadministration of PMA in vitro. CONCLUSION: These results suggest that NO plays a role in spleen lymphocyte apoptosis in MRL/lpr mice, possibly via inhibition of PKC, despite a Fas defect.

Animals↗