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Concept: White pulp

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Aim: The aim of this study is to ascertain the high somatostatin receptor (SSTR) uptake in spleen and to compare the uptake in spleen and splenosis using SSTR PET/CT using( 68)Ga-DOTATOC. Materials and Methods: SUV(max) of spleen on (68)Ga-DOTATOC SSTR PET/CT (acquired for initial staging) in 10 patients with known neuroendocrine neoplasm of pancreatic tail was analyzed. All patients underwent left pancreatectomy and splenectomy. Diagnosis of splenosis was confirmed on CT, and SUV(max) was noted on follow-up SSTR PET/CT. Results: SUV(max)was 28.8 ± 12.5 in normal spleen and 10.5 ± 4.3 in splenosis. Conclusion: The high uptake of( 68)Ga-DOTATOC (which has a high affinity to SSTR 2) in the spleen as compared to splenosis, which has a different histology, suggests white pulp as the probable site of high SSTR 2 expression.

Concepts: Cancer, Neuroendocrine tumor, Pancreatic cancer, Spleen, Somatostatin, The UpTake, Somatostatin receptor, White pulp

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Although almost any non-Hodgkin lymphoma can involve the spleen or an extranodal site as part of more widely disseminated disease, there is a group of small B-cell lymphomas that specifically arise in these locations. These are important to recognise as some appear to have a behaviour and prognosis that is distinct from their nodal counterparts. In addition, there are entities that are specific to extranodal locations (such as extranodal marginal zone lymphoma) and to the red or white pulp of the spleen. In this review, the characteristics of these entities will be presented as well as clues to help distinguish lymphoma from reactive infiltrates in extranodal sites and measure to distinguish between small B-cell lymphomas encountered in the spleen and at extranodal locations.

Concepts: Types of cancer, Lymphoma, Lymphatic system, Spleen, B-cell lymphoma, Marginal zone, T-cell lymphoma, White pulp

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We have reconstructed small parts of capillary networks in the human splenic white pulp using serial sections immunostained for CD34 alone or for CD34 and CD271. The three-dimensional (3D) models show three types of interconnected networks: a network with very few long capillaries inside the white pulp originating from central arteries, a denser network surrounding follicles plus periarterial T-cell regions and a network in the red pulp. Capillaries of the perifollicular network and the red pulp network have open ends. Perifollicular capillaries form an arrangement similar to a basketball net located in the outer marginal zone. The marginal zone is defined by MAdCAM-1+ marginal reticular stromal cells. Perifollicular capillaries are connected to red pulp capillaries surrounded by CD271+ stromal capillary sheath cells. The scarcity of capillaries inside the splenic white pulp is astonishing, as non-polarised germinal centres with proliferating B-cells occur in adult human spleens. We suggest that specialized stromal marginal reticular cells form a barrier inside the splenic marginal zone, which together with the scarcity of capillaries guarantees the maintenance of gradients necessary for positioning of migratory B- and T-lymphocytes in the human splenic white pulp.

Concepts: Blood, Hematology, T cell, Lymphatic system, Spleen, Marginal zone, Red pulp, White pulp

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The pathogenesis of highly pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV) remains poorly understood. In a previous study, we established an hDPP4-transgenic (hDPP4-Tg) mouse model in which MERS-CoV infection causes severe acute respiratory failure and high mortality accompanied by an elevated secretion of cytokines and chemokines. Since excessive complement activation is an important factor that contributes to acute lung injury after viral infection, in this study, we investigated the role of complement in MERS-CoV-induced lung damage. Our study showed that complement was excessively activated in MERS-CoV-infected hDPP4-Tg mice through observations of increased concentrations of the C5a and C5b-9 complement activation products in sera and lung tissues, respectively. Interestingly, blocking C5a production by targeting its receptor, C5aR, alleviated lung and spleen tissue damage and reduced inflammatory responses. More importantly, anti-C5aR antibody treatment led to decreased viral replication in lung tissues. Furthermore, compared with the sham treatment control, apoptosis of splenic cells was less pronounced in the splenic white pulp of treated mice, and greater number of proliferating splenic cells, particularly in the red pulp, was observed. These data indicate that (1) dysregulated host immune responses contribute to the severe outcome of MERS; (2) excessive complement activation, triggered by MERS-CoV infection, promote such dysregulation; and (3) blockade of the C5a-C5aR axis lead to the decreased tissue damage induced by MERS-CoV infection, as manifested by reduced apoptosis and T cell regeneration in the spleen. Therefore, the results of this study suggest a new strategy for clinical intervention and adjunctive treatment in MERS-CoV cases.

Concepts: Immune system, Inflammation, Bacteria, Blood, Severe acute respiratory syndrome, Spleen, Red pulp, White pulp

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Ebulin f is a ribosome-inactivating protein (RIP) present in green fruits of the dwarf elder (Sambucus ebulus L). Since dwarf elder fruits are used for food and as a medicine, we assessed the study of toxicological effects and safety of ebulin f in elderly mice, comparing these results with those reported in young animals and with other RIPs. Female Swiss mice aged 6 and 12 months of age were intraperitoneally injected with a single dose from 1.4 to 4.5 mg/kg ebulin f. Heart, stomach, intestines, lung, kidney, liver, spleen, pancreas, adrenal gland, uterus, ovary and brain were studied. Histology analysis was carried out by staining with hematoxylin and eosin and Masson’s trichrome observed with a light microscope, or apoptosis detection by TUNEL method observed with a confocal laser microscope. Treated animals injected with the lower dose could recover their weights, but after 14 days half of them died. The higher dose caused a progressive loss of body weight leading to death. In the animals of the experimental groups it was found atrophy of Lieberkühn’s crypts, pneumonia, nephronal degeneration, myocardial atrophy, centrolobular hepatic necrosis, splenic white pulp necrosis foci and increased rate of apoptosis in the intestines and liver, in which apoptoses were mainly located in the vicinity of the lobular central vein. We conclude that ebulin f affects vital organs in elderly mice.

Concepts: Death, Heart, Histology, Organ, Peritoneum, Organs, Endocrine gland, White pulp

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The spleen is one of the main affected organs in canine visceral leishmaniasis (CVL). Disorganization of the splenic white pulp (SWP) has been associated with immunosuppression and disease progression. This study aims to assess structural and cellular changes in the splenic extracellular matrix of dogs with CVL, correlating these changes with the parasite load and clinical signs. Splenic fragments were collected from 41 naturally infected animals for parasite load quantification by quantitative PCR, histopathological analysis and immunohistochemistry for CD3+, CD4+, and CD8+ T cells; CD21+ B cells; Ki-67+, IFN-γ+, and IL-10+ cells; and the MMP-9 and ADAM-10 enzymes. Laminin, collagen and fibronectin deposition were also evaluated. The animals were grouped according to the level of SWP organization. SWP disorganization was accompanied by a reduction in the quantity of lymphoid follicles/mm2 (p > 0.0001). Animals with moderate to intense SWP disorganization showed more clinical signs (p = 0.021), higher laminin (p = 0.045) and collagen deposition (p = 0.036), higher MMP-9 expression (p = 0.035) and lower numbers of CD4+ T cells (p = 0.027) in the spleen than the animals with organized SWP. These data suggest that splenic structure and function are drastically altered and compromised during CVL.

Concepts: White blood cell, Wound healing, Extracellular matrix, Lymphatic system, Spleen, Splenomegaly, Integrin, White pulp

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We previously reported that mice intracerebrally inoculated with the mouse-adapted scrapie strain ME7 have markedly diminished T zones in the spleen due to the decreased expression of CCL19 and CCL21. In addition, follicular dendritic cell networks in germinal centers were larger in ME7-infected spleens compared to uninfected spleens. As an extension of that study, we set out to determine how ME7 infection affects spleen structure and follicular helper T (Tfh) cell responses in mice. For this study, mice were intraperitoneally inoculated with brain homogenate of the ME7 inoculum and spleens were analyzed 50, 130, and 200 days after inoculation and compared with those from uninfected mice. The result showed that ME7- infected mice had increased Tfh cell responses which were maintained until end-stage prion disease. Although CD4 T cells decreased in white pulps, they increased in germinal centers, and expressed higher levels of the Tfh-related genes, such as Bcl6, Il21, Cxcr5, Icos, and Pdcd1. In addition, ME7-infected spleens had increased numbers of CD4 memory T cells. These data indicate that although ME7 infection led to impaired splenic white pulp structure, CD4 memory T cells were increased and Tfh cell responses were required and prolonged to provide help for the replication and accumulation of pathogenic prion protein in germinal centers.

Concepts: Immune system, White blood cell, Monocyte, Gene, Lymphatic system, Dendritic cell, Spleen, White pulp

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T and B cell compartmentalization is a hallmark of secondary lymphoid organs and is maintained by chemokine-expressing stromal cells. How this stromal cell network initially develops and differentiates into two distinct subsets is poorly known, especially for the splenic white pulp (WP). Here, we show that perivascular fibroblast precursors are triggered by LTα1β2 signals to expand, express CCL19/21, and then differentiate into two functionally distinct fibroblast subsets responsible for B and T cell clustering and WP compartmentalization. Failure to express or sense CCL19 leads to impaired T zone development, while lack of B cells or LTα1β2 leads to an earlier and stronger impairment in WP development. We therefore propose that WP development proceeds in multiple steps, with LTα1β2+ B cells acting as major inducer cells driving the expansion and gradual differentiation of perivascular fibroblasts into T and B zone organizer cells.

Concepts: DNA, Protein, Wound healing, Cellular differentiation, Organ, Lymphatic system, Spleen, White pulp

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Acid secretion containing sulfuric and hydrochloric acids is a fascinating defensive phenomenon within many groups of marine organisms. This study aimed to investigate the mice spleen histology and immunotoxicity using skin acid secretion (SAS) of the sea slug Berthellina citrina after oral administration. The spleen showed atrophy in the white pulp, decrease in the splenocytes density, megakaryocytes cytoplasmic degeneration as well as inflammatory cells infiltrations. The white and red pulp splenocytes number decreased time-dependently in the treated spleens. Additionally, the size of the megakaryocytes increased as compared with the control. The administration with SAS increased the number of the IgA(+) cells aggregation in the splenic red pulp. Furthermore, after 7days of the administration, large number of dispersed IgA(+) cells were distributed in splenic parenchyma. The IgA(+) cells numbers increased time-dependently as compared with those in the control. The aggregation sizes and number of the F4/80(+) cell in the splenic red pulp were increased. Furthermore the F4/80(+) cells numbers increased time-dependently as compared with those in the control. The UEAI(+) cells were found as free cells but not in aggregations in the control splenic red pulp. Contradictory to the number of IgA(+) cells and F4/80(+) cells the number of the UEAI(+) cells decreased time-dependently after administration with SAS. Hematologically, abnormal numbers of WBCs different cells were observed after administration with SAS. This study provides new insight about the toxicity of a marine extract may be used in natural products industry or medical applications.

Concepts: Cell, Hematology, Lymphatic system, Spleen, Gastric acid, Marginal zone, Red pulp, White pulp

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The immunomodulatory effect of triterpene glycoside cucumarioside A2-2 (CA2-2), isolated from the Far Eastern sea cucumber Cucumaria japonica, on the mouse spleen was investigated in comparison with lipopolysaccharide (LPS). It has been shown that the intraperitoneal (i.p.) glycoside administration did not influence on splenic weights, while the statistically significant increase in splenic weight was observed after LPS administration. Changes in the ratio of red to white pulp after CA2-2 or LPS administration were observed. The proportion of splenic white pulp after glycoside or LPS administration increased by up to 34% and 36%, respectively. A detailed study of the distribution of the РСNA (Proliferating Cell Nuclear Antigen) marker showed that the proliferative activity in the white pulp under CA2-2 and LPS influence increased 2.07 and 2.24 times, respectively. The localization of PCNA-positive nuclei in the white pulp region, as well as their dimensional characteristics, suggests that a large proportion of the proliferating cell population consisted of B cells. The mass spectrometry profiles of spleen peptide/protein homogenate were obtained using the MALDI-TOF-MS (Matrix -Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry) approach. It was found that i.p. stimulation of animals with CA2-2 or LPS leads to marked changes in the intensity of revealed characteristic peaks of peptides/proteins after exposure to immunostimulants.

Concepts: Ratio, Spleen, White pulp