Periarteriolar Lymphatic Sheath Research Articles

Aflatoxin B1 administration causes inflammation and apoptosis in the lungs and spleen

Aflatoxin is a naturally occurring mycotoxin that has numerous toxic effects. The main aim of the present study was to evaluate the toxic effects of aflatoxin B1 (AFB1) on the lungs and spleen. Mice were repeatedly exposed to AFB1 (0.3 mg/kg body weight) on alternate days for four weeks via oral route. The histopathological data in AFB1-treated mice show alveolar epithelial hyperplasia with inflammation and the presence of numerous alveolar macrophages with minimal hemorrhage. There was an increase in vascular neutrophils and interstitial inflammation. The branching of vessels was plugged with neutrophils. AFB1 administration also causes splenomegaly. The AFB1-treated spleen shows the tingible body macrophages (TBM) scattered within the splenic white pulp. Apoptosis may lead to atrophy in a selected region of the white pulp area. There is a decrease in cellularity within the periarteriolar lymphatic sheath (PALS). The inflammation causes the congestion of red pulp with the increase in nuclear debris, and vacuoles are also visible. The flow cytometry data further suggests enhanced apoptosis in lung and spleen cells.

Acalypha wilkesiana Exhibits Antihyperglycemic Potentials and Ameliorates Damages to Pancreas and Spleen of Diabetic Rat Model

Background: The present study investigated the antihyperglycemic and ameliorative effect of aqueous leaves extract of Acalypha wilkesiana on alloxan-induced diabetic male rats. The experimental rats were divided into six groups. Rats of the first group served as normal controls. Rats of the second group were negative control as they were induced with diabetes without treatment. The third group was treated with glibenclamide after induction of diabetes. The fourth, fifth and sixth groups were diabetic rats, treated with aqueous leaves extract of Acalypha wilkesiana at low dose (100mg/kg body weight), medium dose (200mg/kg body weight) and high dose (400mg/kg body weight) respectively. The blood glucose levels of the animals in each group were checked on day 5, 10 and 15 to examine the antihyperglycemic effect of the aqueous leaves extract of Acalypha wilkesiana. Also, on day 5, 10 and 15, the pancreas and spleen of experimental animals from each group were harvested for histological examination. Result: The result obtained showed that the graded doses of the extract significantly (p<0.05) reduced the blood glucose levels of the diabetic animals in a dose-dependent manner. Also, the histological examination of the pancreas and spleen of the experimental animals treated with aqueous leaves extract of Acalypha wilkesiana showed normal pancreatic islet (PI) filled with islet cells (Granular appearance) and pancreatic acini (PA), while normal spleen with white pulp containing periarteriolar lymphatic sheath (PALS) and central arteriole (CA), splenic cord (SC) and sinusoids (SS) were seen in the same animals treated with the extract. The effect of the extract was similar in action to the standard drug glibenclamide. Conclusion: The aqueous leaves extract of Acalypha wilkesiana possesses antihyperglycemic potentials and ameliorates the pancreas and spleen of diabetic albino rats.

Anti-Leishmania infantum Antibody-Producing Plasma Cells in the Spleen in Canine Visceral Leishmaniasis.

The spleen is involved in visceral leishmaniasis immunopathogenesis, and presents alterations in white-pulp microenvironments that are associated with an increased susceptibility to coinfections and patient death. Plasmacytosis in splenic red pulp (RP) is one observed alteration, but the specificity of antibody-secreting cells and the distribution of them has not yet been evaluated. We biotinylated soluble L. infantum membrane antigens (bSLMA) used as probes in modified immunohistochemistry, and detected the presence of anti-L. infantum antibody-secreting cells. Were used spleens from eight dogs from the endemic area for canine visceral leishmaniasis (CanL), and three healthier controls. The spleen sections were cryopreserved, and we performed modified immunohistochemistry. The ratio of plasma cells which were reactive to bSLMA (Anti-Leish-PC) in the spleen RP and periarteriolar lymphatic sheath (PALS) were calculated. Dogs with CanL present hyperglobulinemia and more plasma cells in their RP than the controls. Furthermore, dogs with CanL presented a lower proportion of Anti-Leish-PC in their RP than in PALS. Likewise, dysproteinemia was related to RP and PALS plasmacytosis, and a more severe clinical profile.

Age-Related Variation in Sympathetic Nerve Distribution in the Human Spleen.

Introduction: The cholinergic anti-inflammatory pathway (CAIP) has been proposed as an efferent neural pathway dampening the systemic inflammatory response via the spleen. The CAIP activates the splenic neural plexus and a subsequent series of intrasplenic events, which at least require a close association between sympathetic nerves and T cells. Knowledge on this pathway has mostly been derived from rodent studies and only scarce information is available on the innervation of the human spleen. This study aimed to investigate the sympathetic innervation of different structures of the human spleen, the topographical association of nerves with T cells and age-related variations in nerve distribution.Materials and Methods: Spleen samples were retrieved from a diagnostic archive and were allocated to three age groups; neonates, 10–25 and 25–70 years of age. Sympathetic nerves and T cells were identified by immunohistochemistry for tyrosine hydroxylase (TH) and the membrane marker CD3, respectively. The overall presence of sympathetic nerves and T cells was semi-automatically quantified and expressed as total area percentage. A predefined scoring system was used to analyze the distribution of nerves within different splenic structures.Results: Sympathetic nerves were observed in all spleens and their number appeared to slightly increase from birth to adulthood and to decrease afterward. Irrespective to age, more than halve of the periarteriolar lymphatic sheaths (PALSs) contained sympathetic nerves in close association with T cells. Furthermore, discrete sympathetic nerves were observed in the capsule, trabeculae and red pulp and comparable to the total amount of sympathetic nerves, showed a tendency to decrease with age. No correlation was found between the number of T cells and sympathetic nerves.Conclusion: The presence of discrete sympathetic nerves in the splenic parenchyma, capsule and trabecular of human spleens could suggest a role in functions other than vasoregulation. In the PALS, sympathetic nerves were observed to be in proximity to T cells and is suggestive for the existence of the CAIP in humans. Since sympathetic nerve distribution shows interspecies and age-related variation, and our general understanding of the relative and spatial contribution of splenic innervation in immune regulation is incomplete, it remains difficult to estimate the anti-inflammatory potential of targeting splenic nerves in patients.

The pathology of the spleen in lethal canine babesiosis caused by Babesia rossi.

To provide useful information based on the macropathology, histopathology and immunohistochemical investigation in the spleens of dogs with Babesia rossi infection. Control spleens were collected from four healthy dogs euthanized for welfare reasons. Nine dogs that died naturally because of a mono-infection with Babesia rossi were selected for the diseased group. One haematoxylin-and-eosin-stained section of splenic tissue from each of the infected and control dogs was examined under the light microscope. Immunohistochemical markers were applied to characterize different immunocyte populations. The application of analytic software enabled semi-quantitative comparison of leucocyte subpopulations. Routine splenic histopathology revealed diffuse intermingling of white and red pulp from infected dogs with a clear loss of distinction between these zones. Immunohistochemistry revealed an increase in the proportion of tissue resident and bone marrow origin macrophages in the infected spleens. Apart from a few remnant lymphocytes within the peri-arteriolar lymphatic sheaths and follicles, the majority of the immunocytes redistributed to the red pulp, supporting the observation of white and red pulp intermingling. The majority of our findings are in agreement with histomorphological descriptions of the spleen in a variety of noncanid mammalian hosts with lethal malaria or babesiosis.

Pro-Cellular Exhaustion Markers are Associated with Splenic Microarchitecture Disorganization and Parasite Load in Dogs with Visceral Leishmaniasis

In canine visceral leishmaniasis (CVL), splenic white pulp (SWP) disorganization has been associated with disease progression, reduced cytokine and chemokine expression and failure to control the parasite load. This profile is compatible with the cellular exhaustion previously shown in human visceral leishmaniasis. The present study aimed to evaluate the in situ expression of cellular exhaustion markers and their relation to clinical signs, SWP disorganization and parasite load. Forty dogs naturally infected by Leishmania infantum were grouped according to levels of SWP organization and parasite load. SWP disorganization was associated with reductions in the periarteriolar lymphatic sheath and lymphoid follicles/mm2 and worsening of the disease. Apoptotic cells expressing CTLA-4+ increased in dogs with disorganized SWP and a high parasite load. In the same group, PD-L1 and LAG-3 gene expression were reduced. A higher number of CD21+TIM-3+ B cells was detected in disorganized spleens than in organized spleens. Apoptosis is involved in periarteriolar lymphatic sheath reduction and lymphoid follicle atrophy and is associated with CTLA-4+ cell reductions in the splenic tissue of dogs with visceral leishmaniasis (VL). Failure to control the parasite load was observed, suggesting that cell exhaustion followed by T and B cell apoptosis plays a role in the immunosuppression observed in CVL.

The novel histological evidence of the blood-spleen barrier in duck (Anas platyrhynchos).

To identify the existence and composition of the blood-spleen barrier (BSB) in ducks, the microanatomical structures of the duck spleen were investigated by light and transmission electron microscopy, silver staining, enzymatic histochemistry and intravenous injection of ink. The endothelial cells of the sheathed capillaries were cuboidal-shaped and surrounded by an ellipsoid consisting of reticular cells, similar to high endothelial venules (HEVs). After ink injection, carbon particles were initially restricted to the ellipsoid and later trapped in the periellipsoidal lymphatic sheaths (PELS), and then transferred to the periarteriolar lymphatic sheaths (PALS) and splenic nodules over time. Reticular fibers were primarily distributed at the basement membrane of the sheathed capillaries and the periphery of the PELS. Macrophages were primarily distributed at the border between red pulp and PELS. These results suggested that the BSB was present in the ellipsoid and PELS and consisted of the mechanical barrier composed of endothelial cells of the sheathed capillaries, reticular cells and reticular fibers and the biological barrier composed of ellipsoid-associated macrophages. In conclusion, the BSB was identified in the duck spleen for the first time, including cuboidal endothelial cells, ellipsoid-associated macrophages, reticular cells and fibers, and resisting circulating pathogen invasions. The study of BSB in ducks provides a theoretical foundation for the structural composition of the avian immune system.

Histogenesis of Human Fetal Spleen

Abstract Background and Aims: Spleen is the largest secondary lymphatic organ. It acts as a graveyard for RBCs, is essential for immune responses, performs lymphopoiesis in adults and haemopoiesis in fetuses. The present study was conducted to assess the histogenesis of spleen in human fetuses in view of existing literature. Material and Methods: The study was carried out on 34 formalin preserved human fetuses procured from Dr Sushila Tiwari Government Hospital, Haldwani with due clearance from ethical committee. The 6 pm sections of the spleen were stained with Haematoxylin and Eosin and observed under light microscope. Results: At 14 tol5 weeks, spleen had extensive sinusoids filled with RBCs and few lymphocytes. At 16-18 weeks, trabecular arteries were noticed more towards centre along with extensive haemopoietic cells in the venous sinusoids. By 20th week lymphocytic aggregation had started around arterioles. By 24 weeks periarteriolar lymphatic sheath was clearly observed. At term (37-40 weeks), classical primary lymphoid follicle was present but germinal centers were not observed. Conclusion: During earlier differentiation, spleen symbolizes the function of haemopoietic activities and gradually during subsequent gestation; it establishes its identity as a principle lymphoid tissue.

In situ hybridization to detect and localize signature cytokines of T-helper (Th) 1 and Th2 immune responses in chicken tissues

The avian immune system has been shown to possess a repertoire of cytokines directing T-helper (Th) 1 and Th2 types of immune responses similar to that in mammals. The objective of this study was to establish in situ hybridization (ISH) for the localization of mRNA of selected signal cytokines, chicken interferon-γ (ChIFN-γ), chicken interleukin (ChIL)-4 and ChIL-13 in fixed tissues. RNA probes were generated to hybridize to 488, 318, and 417bp of the respective target mRNA. Probe concentrations ranging from 100ng/ml to 400ng/ml were shown to be suitable to label cells that expressed these cytokines. The specificity of every probe was verified using the respective sense probe. ChIFN-γ, ChIL-4 and ChIL-13 positive cells were observed in the lymphocytic infiltrations of liver and in the periarteriolar lymphatic sheaths of spleen collected from specific-pathogen-free chickens. ISH of these cytokines in a severely inflamed liver due to infiltration with the parasite Histomonas meleagridis revealed the expression of both ChIFN-γ and ChIL-13 mRNA in the mononuclear infiltrates. In conclusion, ChIFN-γ, ChIL-4 and ChIL-13 mRNA were efficiently localized by ISH, which supplies a valid technique to characterize immune responses in fixed tissues.

Human spleen microanatomy: why mice do not suffice.

The microanatomical structure of the spleen has been primarily described in mice and rats. This leads to terminological problems with respect to humans and their species-specific splenic microstructure. In mice, rats and humans the spleen consists of the white pulp embedded in the red pulp. In the white pulp, T and B lymphocytes form accumulations, the periarteriolar lymphatic sheaths and the follicles, located around intermediate-sized arterial vessels, the central arteries. The red pulp is a reticular connective tissue containing all types of blood cells. The spleen of mice and rats exhibits an additional well-delineated B-cell compartment, the marginal zone, between white and red pulp. This area is, however, absent in human spleen. Human splenic secondary follicles comprise three zones: a germinal centre, a mantle zone and a superficial zone. In humans, arterioles and sheathed capillaries in the red pulp are surrounded by lymphocytes, especially by B cells. Human sheathed capillaries are related to the splenic ellipsoids of most other vertebrates. Such vessels are lacking in rats or mice, which form an evolutionary exception. Capillary sheaths are composed of endothelial cells, pericytes, special stromal sheath cells, macrophages and B lymphocytes. Human spleens most probably host a totally open circulation system, as connections from capillaries to sinuses were not found in the red pulp. Three stromal cell types of different phenotype and location occur in the human white pulp. Splenic white and red pulp structure is reviewed in rats, mice and humans to encourage further investigations on lymphocyte recirculation through the spleen.

Identification and structural composition of the blood–spleen barrier in chickens

To identify the existence and composition of the blood–spleen barrier (BSB) in chickens, the microanatomical features of the spleen were investigated by light and transmission electron microscopy, intravenous injection of ink, acid phosphatase reaction, and silver impregnation. The results showed that the white pulp in chicken spleen consists of lymphoid nodules, periarteriolar lymphatic sheaths (PALS) and periellipsoidal lymphatic sheaths (PELS). There was no evidence for the presence of a marginal zone.The splenic ellipsoid was a unique structure, which functioned as a barrier for filtering and phagocytosis. Uptake of carbon particles was limited to the ellipsoid and PELS, 60 min after injection of carbon particles. Reticular fibres were densely distributed in the ellipsoid and extended into the PELS. Ellipsoid-associated cells (EACs), reticular cells and macrophages were acid phosphatase positive. The sheathed capillaries, surrounded by the ellipsoid, were similar to high endothelial venules (HEVs). These findings suggest that the BSB of chickens is present in the ellipsoid and PELS, protecting the spleen from invasion from circulating pathogens. The BSB was a reticular framework, between the arterial and venous vessels, which included cuboidal-shaped endothelial cells, supporting cells, EACs, macrophages, reticular cells and fibres. Lymphocyte migration into the spleen parenchyma is most likely via the HEV-like vessels. These research findings contribute to better understanding of avian immunology and provide an insight into evolutionary differences in the immune system.

Retrospection to discovery of bursal function and recognition of avian dendritic cells; past and present

In 1954 the discovery of bursal function was one of the major contributions to the formation of the T and B cell concept of immunology. In 1978 the avian dendritic cells; bursal secretory dendritic cell (BSDC) and follicular dendritic cell (FDC) in the cecal tonsil were recognized. In 1982 the interdigitating dendritic cell was described in the periarteriolar lymphatic sheath (PALS) of the spleen. This paper is a retrospection of the stories of the discovery of bursal function and recognition of avian dendritic cells and includes the markers which can be used for monitoring and characterizing avian dendritic cells.

Histomorphology of the Spleen in the Fox (Vulpes bengalensis)

1- Pylorus. 2- Craniodorsaltenuis muscle. 3- Proximal region of the descending limb of the duodenum 3- Pancreatico- duodenal artery Right branch of Celiac artery 1-Duodenum 2-Pancrease 4- Ileocecal artery Pancreaticoduodenal artery 1- 1-Distal (cranial) two thirds of the left cecom 2- and adjacent ileum 5- Colic branch Cranial mesenteric artery 1- Cranial portion of the colon Abstract The spleen is the largest secondary lymphatic organ involved in filtering the blood and initiating immune re- sponses against blood borne anti- gens. The present study was carried out on the spleen of fox collected from the Department of Veterinary Pathology. Grossly, spleen was tongue shaped and dark brown in colour. It was located in the left cra- nial quadrant of the abdomen. His- tologically, the spleen was sur- rounded by a thick capsule com- posed mainly of dense collagen fi- bers with a few smooth muscle fi- bers. Thick trabeculae consisting of collagen, few elastic and smooth muscle fibers extended from the capsule into the parenchyma. The splenic parenchyma was composed of red pulp with extensive venous sinuses, venules and spleniccords. White pulp was distributed through- out the spleen and was composed of lymphatic nodules with a central artery, and diffuse lymphatic tissue arranged as periarteriolar lymphatic sheaths (PALS).

167. Long-term effects of total body irradiation on sympathetic innervation of the murine spleen

Previous studies in mice have shown that total body irradiation (TBI) leads to splenic atrophy, acute reductions in splenic leukocyte populations, and changes in phagocytic function. We also reported that many TBI-induced changes in splenic phagocytic populations were mitigated by chlorisondamine, a non-selective nicotinic blocker, suggesting sympathetic control. To characterize the long-term effects associated with TBI on the noradrenergic sympathetic innervation of the spleen, female, 9–10 week-old C57BL/6J mice were irradiated with Co-60 gamma-rays (0–2 Gy) and euthanized 6 months later. Sucrose–potassium phosphate–glyoxylic acid (SPG) histofluorescence staining and HPLC were used to examine splenic noradrenergic innervation and neurochemical concentration of catecholamines, respectively. All samples of the spleen were taken distal to the hilus. Fluorescence histochemistry for catecholamines revealed no change in the distribution of fluorescent nerves in the splenic white pulp in irradiated mice compared with controls. However, the density of sympathetic nerves coursing along the central arterioles and extending into the periarteriolar lymphatic sheath was greater in mice irradiated at 2 Gy compared with non-irradiated controls. The white pulps also appeared to be reduced in spleens from this group. While norepinephrine concentrations did not differ from control values, dopamine concentrations were reduced. Collectively, these findings suggest maintained nerve distribution in a reduced volume of white pulp in irradiated mice, and increased norepinephrine release and availability for target cells of the immune system.

Origin of the chicken splenic reticular cells influences the effect of the infectious bursal disease virus on the extracellular matrix

The effects of infectious bursal disease virus (IBDV) (strain F52/70) infection were studied by immunohistochemical methods on the splenic extracellular matrix (ECM). The major fibrillar components of the ECM, the type I and type III collagens and the main ECM organizing glycoproteins (laminin, tenascin and fibronectin) were monitored up to 11 days post-infection (d.p.i.). By 3 d.p.i., the collagens that form the basic scaffold of the antigen-trapping region of the spleen are destroyed, which is followed by deterioration of the glycoproteins. The ECM in the red pulp and the other regions of the white pulp (periarteriolar lymphatic sheath and germinal centre) seem to be normal. The reason for the significantly different pathological alterations in the ECM between the two regions of the spleen may be explained by the origin of the reticular cells. The reticular cells in the antigen-trapping zone and other splenic regions are of haemopoietic and mesenchymal origins, respectively. Possibly, the reticular cells of the haemopoietic origin are more susceptible for the IBDV infection than the mesenchymal ones. Development of the antigen-trapping, B-cell-dependent zone of the splenic white pulp precedes that of the periarteriolar lymphatic sheath and germinal centre, which suggests that this region may contribute to B-cell maturation. Damage of the ECM in the antigen-trapping zones results in impairment of tissue organization, which may contribute to the permanent immunosuppression.

Diffuse lymphangiomatous hyperplasia of the spleen with hyaline bodies. A pseudotumoral proliferation arising from the lymphatic vessels of the periarteriolar lymphatic sheath

Diffuse lymphangiomatous hyperplasia of the spleen with hyaline bodies. A pseudotumoral proliferation arising from the lymphatic vessels of the periarteriolar lymphatic sheath

Trypanosoma cruzi infection induces a massive extrafollicular and follicular splenic B-cell response which is a high source of non-parasite-specific antibodies

Acute infection with Trypanosoma cruzi, the aetiological agent of Chagas' disease, results in parasitaemia and polyclonal lymphocyte activation. It has been reported that polyclonal B-cell activation is associated with hypergammaglobulinaemia and delayed parasite-specific antibody response. In the present study we analysed the development of a B-cell response within the different microenvironments of the spleen during acute T. cruzi infection. We observed massive germinal centre (GC) and extrafollicular (EF) responses at the peak of infection. However, the EF foci were evident since day 3 post-infection (p.i.), and, early in the infection, they mainly provided IgM. The EF foci response reached its peak at 11 days p.i. and extended from the red pulp into the periarteriolar lymphatic sheath. The GCs were detected from day 8 p.i. At the peak of parasitaemia, CD138(+) B220(+) plasma cells in EF foci, red pulp and T-cell zone expressed IgM and all the IgG isotypes. Instead of the substantial B-cell response, most of the antibodies produced by splenic cells did not target the parasite, and parasite-specific IgG isotypes could be detected in sera only after 18 days p.i. We also observed that the bone marrow of infected mice presented a strong reduction in CD138(+) B220(+) cells compared with that of normal mice. Hence, in acute infection with T. cruzi, the spleen appears to be the most important lymphoid organ that lodges plasma cells and the main producer of antibodies. The development of a B-cell response during T. cruzi infection shows features that are particular to T. cruzi and other protozoan infection but different to other infections or immunization with model antigens.

Architecture of the Blood‐Spleen Barrier in the Soft‐Shelled Turtle, Pelodiseus Sinensis

We investigated the structure of the soft-shelled turtle, Pelodiseus sinensi, spleen and demonstrated that there were several microanatomical peculiarities by light and transmission electron microscopy. In the spleen, the white pulp of the spleen was composed of two compartments, the periarteriolar lymphatic sheath (PALS) and periellipsoidal lymphatic sheath (PELS). No lymph nodules and marginal zones were found. The spleen-blood barrier stood in the PELS and the ellipsoid. The high endothelial lining of penicilliform capillary contained small channels. These channels allowed circulating substances or lymphocytes to enter the ellipsoid. The distal portion of the penicilliform capillaries directly opened to pulp cords. The ellipsoid-associated cell (EAC) was located at the surface of the ellipsoid. Reticular fibers were mainly distributed in ellipsoid and the outer PELS. Both reticular cells and macrophages were distributed in the outer layers of PELS. S-100 protein positive dendritic cells were mainly distributed in out cells layer of the PELS and all over the PALS. Forty minutes after injection, carbon particles of Indian ink were mainly observed in the ellipsoid. Few carbon particles were observed in the outer PELS and fewer carbon particles in the red pulp. These findings suggested that a blood-spleen barrier indeed existed in the soft-turtle, P. sinensi, and it was a complex composed of an ellipsoid (including supporting cells, EAC, and reticular fibers) and the outer compartments of PELS (including dendritic cells, reticular fibers and cells, macrophages).

Toxicological Effects of In Utero and Lactational Exposure of Rats to a Mixture of Environmental Contaminants Detected in Canadian Arctic Human Populations

As part of the program to investigate mixture effects of environmental pollutants, this study describes clinical, biochemical, and histopathological effects in rats perinatally exposed to a mixture of persistent organochlorine pollutants and methylmercury that simulates the blood contaminant profile of humans residing in the Canadian Arctic. Groups of pregnant rats were administered orally 0, 0.05, 0.5, or 5 mg/kg body weight (bw)/d of a reconstituted mixture of organochlorine pollutants (referred to as mixture hereafter) from gestational day (GD) 1 to postnatal day (PND) 23. Positive and vehicle controls were given Aroclor 1254 (Aroclor hereafter, 15 mg/kg bw) and corn oil (vehicle), respectively. After parturition, the pups were colled to 8 per litter on PND 4, and killed on PND 35, 77, or 350, when tissues were collected for analysis. Gestational and lactational exposure of rats to mixture up to 5 mg/kg bw produced adverse effects in the offspring, including growth suppression, decreased spleen and thymic weights, increased serum cholesterol and liver microsomal enzyme activities, lower liver retinoid levels, and histological changes in the liver, thyroid, and spleen. Histological changes in the liver consisted of hepatic inflammation, vacuolation, and hypertrophy, while alterations in the thyroid were characterized by hypertrophy and hyperplasia of follicles. The hepatic and thyroidal effects were mild even at the highest dose. The spleen showed a dose-dependent atrophy in the lymphoid nodules and periarteriolar lymphatic sheath regions. Aroclor produced effects similar to those seen in the highest mixture group. In summary, this study demonstrates that exposure to the reconstituted mixture at 5 mg/kg bw produced growth suppression, changes in organ weights, and biochemical and histopathological changes in liver, thyroid, and spleen. This study also demonstrated that the blood level in rats given the 5-mg/kg dose, where most of the effects were observed, is 100-fold higher than the blood level in the 0.05-mg/kg group, which is comparable to that found in humans living in the Canadian Arctic region.

Neuritogenic Effects of T Cell-Derived IL-3 on Mouse Splenic Sympathetic Neurons In Vivo

To determine the role played by lymphocytes and cytokines in the growth of sympathetic neurons in vivo, the innervation and cytokine levels were examined in the spleens of SCID mice that lack T and B cells. Splenic noradrenaline, nerve growth factor (NGF), and IL-1beta levels were elevated in SCID mice. Immunohistochemical examination revealed that the density of tyrosine hydroxylase-positive (TH(+)) fibers of splenic central arteries in SCID mice was increased compared with wild-type C.B-17 mice, while SCID mice had significantly fewer TH(+) fibers in their periarteriolar lymphatic sheaths (PALS). Two weeks after SCID mice were injected with C.B-17 splenic T cells, their TH(+) fiber staining increased in the PALS. IL-3 levels increased significantly in SCID mice following T cell reconstitution, and the administration of anti-IL-3 Ab blocked the above T cell-induced increase in innervation in the PALS. Anti-IL-3 treatment also inhibited the regeneration of splenic sympathetic neurons in C.B-17 mice after they were chemically sympathetomized with 6-hydroxydopamine. Depletion of NK cells by anti-asialo GM1 promoted the splenic innervation in SCID mice, while there were no significant changes in the innervation between CD8(+) T cell-deficient beta(2)-microglobulin knockout mice and their wild type. Our results suggest that T cells (probably CD4(+) Th cells but not CD8(+) CTLs) play a role in regulating the sympathetic innervation of the spleen; this effect appeared to be mediated, at least in part, by IL-3. On the contrary, NK cells may exert an inhibitory effect on the sympathetic innervation.