red pulp
Recently Published Documents


TOTAL DOCUMENTS

308
(FIVE YEARS 74)

H-INDEX

34
(FIVE YEARS 3)

Pathogens ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1635
Author(s):  
Jonathan L. M. Fontes ◽  
Bianca R. Mesquita ◽  
Reginaldo Brito ◽  
Juliana C. S. Gomes ◽  
Caroline V. B. de Melo ◽  
...  

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.


2021 ◽  
Vol 28 (6) ◽  
pp. 5148-5154
Author(s):  
Elif Yilmaz ◽  
Arashpreet Chhina ◽  
Victor E. Nava ◽  
Anita Aggarwal

Splenic diffuse red pulp small B-cell lymphoma (SDRPL) is a rare disease, representing <1% of all non-Hodgkin lymphomas (NHL). The most common clinical manifestations include splenomegaly, lymphocytosis, and hemocytopenia. A diagnosis of SDRPL can be challenging, as it shares multiple clinical and laboratory features with splenic marginal zone lymphoma (SMZL), hairy cell leukemia (HCL), and HCL variant (HCL-v). Obtaining splenic tissue remains the gold standard for diagnosis. In the cases where splenic tissue is not available, diagnosis can be established by a review of peripheral blood and bone marrow studies. SDRPL is characterized by a diffuse involvement of the splenic red pulp by monomorphous small-to-medium sized mature B lymphocytes effacing the white pulp. The characteristic immunophenotype is positive for CD20, DBA.44 (20 to 90%), and IgG, and typically negative for CD5, CD10, CD23, cyclin D1, CD43, annexin A1, CD11c, CD25, CD123, and CD138. The Ki-67 proliferative index is characteristically low. Cyclin D3 is expressed in the majority of SDRPL in contrast with other types of small B-cell lymphomas, thus facilitating the recognition of this disease. There is no standard treatment regimen for SDRPL. Initial treatment options include splenectomy, rituximab monotherapy, or a combination of both. Chemoimmunotherapy should be considered in patients with advanced disease at baseline or progression.


2021 ◽  
Vol 28 (6) ◽  
pp. 5124-5147
Author(s):  
John J. Schmieg ◽  
Jeannie M. Muir ◽  
Nadine S. Aguilera ◽  
Aaron Auerbach

CD5-negative, CD10-negative low-grade B-cell lymphoproliferative disorders (CD5-CD10-LPD) of the spleen comprise a fascinating group of indolent, neoplastic, mature B-cell proliferations that are essential to accurately identify but can be difficult to diagnose. They comprise the majority of B-cell LPDs primary to the spleen, commonly presenting with splenomegaly and co-involvement of peripheral blood and bone marrow, but with little to no involvement of lymph nodes. Splenic marginal zone lymphoma is one of the prototypical, best studied, and most frequently encountered CD5-CD10-LPD of the spleen and typically involves white pulp. In contrast, hairy cell leukemia, another well-studied CD5-CD10-LPD of the spleen, involves red pulp, as do the two less common entities comprising so-called splenic B-cell lymphoma/leukemia unclassifiable: splenic diffuse red pulp small B-cell lymphoma and hairy cell leukemia variant. Although not always encountered in the spleen, lymphoplasmacytic lymphoma, a B-cell lymphoproliferative disorder consisting of a dual population of both clonal B-cells and plasma cells and the frequent presence of the MYD88 L265P mutation, is another CD5-CD10-LPD that can be seen in the spleen. Distinction of these different entities is possible through careful evaluation of morphologic, immunophenotypic, cytogenetic, and molecular features, as well as peripheral blood and bone marrow specimens. A firm understanding of this group of low-grade B-cell lymphoproliferative disorders is necessary for accurate diagnosis leading to optimal patient management.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Joern Pezoldt ◽  
Carolin Wiechers ◽  
Florian Erhard ◽  
Ulfert Rand ◽  
Tanja Bulat ◽  
...  

AbstractOur understanding of the composition and functions of splenic stromal cells remains incomplete. Here, based on analysis of over 20,000 single cell transcriptomes of splenic fibroblasts, we characterized the phenotypic and functional heterogeneity of these cells in healthy state and during virus infection. We describe eleven transcriptionally distinct fibroblastic cell clusters, reassuring known subsets and revealing yet unascertained heterogeneity amongst fibroblasts occupying diverse splenic niches. We further identify striking differences in innate immune signatures of distinct stromal compartments in vivo. Compared to other fibroblasts and to endothelial cells, Ly6C+ fibroblasts of the red pulp were selectively endowed with enhanced interferon-stimulated gene expression in homeostasis, upon systemic interferon stimulation and during virus infection in vivo. Collectively, we provide an updated map of fibroblastic cell diversity in the spleen that suggests a specialized innate immune function for splenic red pulp fibroblasts.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1989-1989
Author(s):  
Anne Davidson ◽  
Naomi Maria ◽  
Julien Papoin ◽  
Chirag Raparia ◽  
Zeguo Sun ◽  
...  

Abstract Anemia is a common hematologic abnormality in patients with active systemic lupus erythematosus (SLE), a disease characterized by innate immune system activation by nucleic acid containing immune complexes and cell debris. Work in mouse models has shown that overactivation of several cytoplasmic innate immune sensors by either self-DNA or self-RNA specifically leads to erythroid cell death in the fetal liver while sparing other hematopoietic cell lineages. The endosomal receptors TLR7 and TLR8 both recognize ssRNA in humans. TLR7 overexpression in mice causes a lupus syndrome that includes the development of mild to moderate anemia (Hb &gt;10) and thrombocytopenia and is associated with spleen histiocytosis, autoimmune hemolysis, erythrophagocytosis and compensatory stress erythropoiesis in the spleen. A recent study demonstrated that patients with TLR8 gain of function mutations present with immunodeficiency, inflammation and bone marrow failure. However the role of TLR8 in SLE has been difficult to study in mice because it has a 5 amino acid deletion that attenuates its RNA binding capacity. To address the role of TLR8 in SLE, we overexpressed human TLR8 in a lupus mouse model (huTLR8tg.Sle1.Yaa) using a BAC transgene. 50% of homozygous huTLR8tg.Sle1.Yaa mice developed severe anemia (Hb&lt;9) resulting in early mortality starting at 3-4.5 months of age. This phenotype required both the Sle1 and Yaa loci that promote the formation of high titer anti-chromatin and anti-RNA antibodies and onset of nephritis at &gt;6 months of age. There was no difference in autoantibody titers between Sle1.Yaa wt and huTLR8tg mice and early death was not due to premature onset of renal disease. All mice had normal RBC indices prior to 10 weeks of age. Anemia was associated with an increase in bone marrow (BM) trabecular bone and a decrease in erythroblastic islands (EBI) in the BM with compensatory stress erythropoiesis leading to reticulocytosis and vast splenomegaly. RBC half-life was normal even after the development of reticulocytosis, but decreased in severely anemic mice as a pre-terminal event. Using CFSE labeling of RBCs we showed that hemophagocytosis occurred in vivo as a result of expansion of phagocytic red pulp macrophages. Flow cytometry of BMs from transgenic mice showed normal erythroid progenitors but a block at the late CFU-E/early proerythroblast stage leading to overall decreased terminal erythroid differentiation. Single cell RNAseq of EBIs isolated from transgenic BMs confirmed the block in erythropoiesis. The erythroblast cluster proximal to the block had a signature of mitochondrial stress and decreased proliferation. Spleen EBIs from transgenic mice were characterized by a low frequency of early erythroblasts compared with BM EBIs. We found 6 related clusters of EBI central macrophages in the BMs of both wt and transgenic mice. In transgenic mice, most of these displayed an inflammatory and Type 1 IFN signature. One cluster (M2) expressed all the classical central macrophage phenotypic markers in wt mice but was characterized in transgenic mice by downregulation of multiple phagocytic receptors and a 5-fold decrease of VCAM1 expression. Loss of VCAM1 and downregulation of CD169 in central macrophages of transgenic BMs was confirmed by flow cytometry. By contrast spleen central macrophages from transgenic mice retained VCAM and CD169 expression. Together, these results suggest that failure of BM erythropoiesis in huTLR8 transgenic SLE.Yaa lupus-prone mice, in which the acquisition of anti-nucleic acid autoantibodies drives excess innate stimulus through TLR7 and huTLR8, is due to a block in differentiation from CFU-E to the early proerythroblast stage; this is associated with an inflammatory phenotype specifically in BM erythroblastic island central macrophages and down regulation of adhesion and phagocytic receptors. Stress erythropoiesis in the spleens is associated with vast expansion of red pulp macrophages with phagocytic properties and fatal anemia is associated with a decrease in red blood cell half-life, suggesting that excessive RBC phagocytosis, coupled with insufficient erythroblast progenitors, eventually exceeds the capability of stress erythropoiesis to replace the RBC mass. Disclosures Kalfa: Agios Pharmaceuticals, Inc.: Other: Steering Committee, Research Funding; FORMA Therapeutics, Inc: Research Funding. Paulson: Forma Therapeutics: Consultancy. Blanc: Keros Therapeutics, Inc.: Consultancy.


2021 ◽  
Author(s):  
Tyng-An Zhou ◽  
Hsuan-Po Hsu ◽  
Yueh-Hua Tu ◽  
Chih-Yu Lin ◽  
Nien-Jung Chen ◽  
...  

Tissue-resident macrophages are essential for protection from pathogen invasion and maintenance of organ homeostasis. The ability of thymic macrophages to engulf apoptotic thymocytes is well appreciated, but little is known about their ontogeny, maintenance, and diversity. Here, we characterized the surface phenotype and transcriptional profile of these cells and found out that they express typical tissue-resident macrophage genes yet also exhibit organ-specific features. Thymic macrophages were most closely related to spleen red pulp macrophages and Kupffer cells and shared the expression of the transcription factor SpiC with these cells. Using shield chimeras, transplantation of embryonic thymuses, and fate mapping, we found that three distinct waves of precursors generate thymic macrophages. Moreover, some of them proliferated in situ. Single-cell RNA sequencing showed that the macrophages in the adult thymus are composed of two populations with distinct localization and origin. Altogether, our work defines the phenotype, origin, and diversity of thymic macrophages.


Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1364
Author(s):  
Patryk Slusarczyk ◽  
Katarzyna Mleczko-Sanecka

The production of around 2.5 million red blood cells (RBCs) per second in erythropoiesis is one of the most intense activities in the body. It continuously consumes large amounts of iron, approximately 80% of which is recycled from aged erythrocytes. Therefore, similar to the “making”, the “breaking” of red blood cells is also very rapid and represents one of the key processes in mammalian physiology. Under steady-state conditions, this important task is accomplished by specialized macrophages, mostly liver Kupffer cells (KCs) and splenic red pulp macrophages (RPMs). It relies to a large extent on the engulfment of red blood cells via so-called erythrophagocytosis. Surprisingly, we still understand little about the mechanistic details of the removal and processing of red blood cells by these specialized macrophages. We have only started to uncover the signaling pathways that imprint their identity, control their functions and enable their plasticity. Recent findings also identify other myeloid cell types capable of red blood cell removal and establish reciprocal cross-talk between the intensity of erythrophagocytosis and other cellular activities. Here, we aimed to review the multiple and emerging facets of iron recycling to illustrate how this exciting field of study is currently expanding.


2021 ◽  
Author(s):  
Hannah L. Raczkowski ◽  
Li S. Xu ◽  
Wei Cen Wang ◽  
Rodney P DeKoter

Spi-C is an E26 transformation-specific transcription factor closely related to PU.1 and Spi-B. Spi-C has lineage-instructive functions important in antibody-generating responses, B cell development, and red pulp macrophage generation. Spi-C is inducible by heme- and NF-κB-dependent pathways in macrophages. The present research aimed to examine the regulation of Spi-C expression in B cells. RT-qPCR analysis revealed that Spic expression was reduced in B cells following addition of lipopolysaccharide, anti-IgM antibodies, CD40L, or cytokines BAFF + IL-4 + IL-5. Cytochalasin treatment partially prevented downregulation of Spic. Unstimulated B cells upregulated Spic over time in culture. To determine the mechanism of Spic regulation, we examined the Spic promoter and upstream regulatory elements. The Spic promoter had unidirectional activity, which was reduced by mutation of an NF-κB binding site. Spic was repressed by an upstream regulatory region interacting with the heme-binding regulator Bach2. Taken together, these data indicate that Spi-C is dynamically regulated by external signals in B cells and provide insight into the mechanism of regulation.


2021 ◽  
Vol 10 (2) ◽  
pp. 30-37
Author(s):  
S. V. Klochkova ◽  
N. T. Alexeeva ◽  
D. B. Nikityuk ◽  
P. M. Torgun ◽  
I. A. Ul'yanov ◽  
...  

The aimof this study was to determine the morphofunctional features of the spleen in rats under immobilization stress and administration of bacterial lipopolysaccharide.Material and methods.60 white Wistar rats were divided into 4 groups. The animals of the first control group were injected with saline. The rats of the second control group were injected with lipopolysaccharide. In the rats of the third group, immobilization stress was induced and the animals of this group were injectedwith saline. In rats of the fourth group, immobilization stress was also caused and lipopolysaccharide was administered in the form of the drug Pyrogenal (Medgamal, Russia) in a dose of 100  µg/kg of body weight. Fragments of the spleen were fixed in a 10% solution of neutral formalin, dehydrated in alcohols of increasing strength, and embedded in paraffin. Thin paraffin sections 4–5 µm thick were stained with hematoxylin and eosin. The area of longitudinal sections  of  the  spleen,  the  area  of  the  white  and red  pulp  were  determined planimetrically.  Using  a  screw  m icrometer eyepiece, the width of the reactive center of the lymph nodes of the white pulp, the width of the mantle and  marginal  zone  of  the  nodules,  as  well  as  the  width  of  the  periarterial  lymphoid sheath  were  measured (40–50 measurements for each animal).Results.It was found that on the 3rd day after the stress morphological signs of a sharp decrease in the activity of the white pulp were revealed. On the 8th day, pronounced recovery processes in the spleen were noted, however, complete restoration of the structure of the spleen did not occur. On the 3rd and 8th days after stress and  administration  of  lipopolysaccharide,  no  signs  of  inhibition  of  the  activity  of  the  white  and  red  pulp  were found in the spleen; morphological parameters of the spleen did not differ from the control values.


Sign in / Sign up

Export Citation Format

Share Document