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Anatomia, Histologia, Embryologia Jul 2019Spleen is one of the important lymphoid organs with wide variations of morphological and physiological functions according to species. Morphology and function of the...
Spleen is one of the important lymphoid organs with wide variations of morphological and physiological functions according to species. Morphology and function of the spleen in bats, which are hosts to several viral strains without exhibiting clinical symptoms, remain to be fully elucidated. This study aims to examine the spleen morphology of fruit bats associated with their physiological functions. Spleen histological observations were performed in three fruit bats species: Cynopterus titthaecheilus (n = 9), Rousettus leschenaultii (n = 3) and Pteropus vampyrus (n = 3). The spleens of these fruit bats were surrounded by a thin capsule. Red pulp consisted of splenic cord and wide vascular space filled with blood. Ellipsoids in all three studied species were found numerously and adjacent to one another forming macrophages aggregates. White pulp consisted of periarteriolar lymphoid sheaths (PALS), lymphoid follicles and marginal zone. The lymphoid follicle contained a germinal centre and a tingible body macrophage that might reflect an active immune system. The marginal zone was prominent and well developed. This study reports some differences in spleen structure of fruit bats compared to other bat species previously reported and discusses possible physiological implications of the spleen based on its morphology.
Topics: Animals; Chiroptera; Spleen
PubMed: 30968443
DOI: 10.1111/ahe.12442 -
Experimental Hematology Sep 2002Hematopoietic stem cells (HSCs) and colony-forming progenitor cells (CFCs) are believed to migrate from liver to bone marrow (BM) around the time of birth, where they...
OBJECTIVE
Hematopoietic stem cells (HSCs) and colony-forming progenitor cells (CFCs) are believed to migrate from liver to bone marrow (BM) around the time of birth, where they remain throughout the animal's life. Although in mice the spleen is also a hematopoietic organ, neither the origin nor the contribution of spleen HSCs to hematopoietic homeostasis has been assessed relative to that of BM HSCs. To investigate these issues we quantitated CFC and HSC activity in the spleen, BM, peripheral blood, and liver of the mouse during ontogeny.
METHODS
CFCs were assessed by clonogenic colony formation, and HSCs by long-term reconstituting ability.
RESULTS
CFCs gradually increased in the BM and decreased in the liver with age. Increased prevalence of CFCs in fetal and pup blood occurred at day (d) 12 postcoitus (pc) and during the period of d16 pc to 4d postbirth, corresponding to the times when hematopoietic cells migrate from the yolk sac and/or aorta-gonad-mesonephros (AGM) to the fetal liver and from the neonatal liver to the BM, respectively. In the spleen, CFCs displayed two peaks of activity at 2d and 14d-15d postbirth. Spleen HSCs also fluctuated during this time period. Neonatal splenectomy did not alter CFC or HSC frequencies in the BM, but CFCs increased in the livers of splenectomized mice.
CONCLUSIONS
These data demonstrate that the liver may act as a site of extramedullary hematopoiesis in the neonate, especially in the absence of the spleen, and imply that the spleen, BM, and liver cooperatively contribute to hematopoietic homeostasis.
Topics: Animals; Animals, Newborn; Aorta; Bone Marrow; Cell Lineage; Cell Movement; Colony-Forming Units Assay; Female; Fetal Blood; Gestational Age; Gonads; Hematopoiesis, Extramedullary; Hematopoietic System; Homeostasis; Liver; Male; Mesonephros; Mice; Mice, Inbred C57BL; Radiation Chimera; Spleen; Splenectomy; Yolk Sac
PubMed: 12225792
DOI: 10.1016/s0301-472x(02)00881-0 -
Human Molecular Genetics Mar 2017Spinal muscular atrophy (SMA) is a progressive neurodegenerative disease that is the leading genetic cause of infantile death. It is caused by a severe deficiency of the...
Spinal muscular atrophy (SMA) is a progressive neurodegenerative disease that is the leading genetic cause of infantile death. It is caused by a severe deficiency of the ubiquitously expressed Survival Motor Neuron (SMN) protein. SMA is characterized by α-lower motor neuron loss and muscle atrophy, however, there is a growing list of tissues impacted by a SMN deficiency beyond motor neurons. The non-neuronal defects are observed in the most severe Type I SMA patients and most of the widely used SMA mouse models, however, as effective therapeutics are developed, it is unclear whether additional symptoms will be uncovered in longer lived patients. Recently, the immune system and inflammation has been identified as a contributor to neurodegenerative diseases such as ALS. To determine whether the immune system is comprised in SMA, we analyzed the spleen and immunological components in SMA mice. In this report, we identify: a significant reduction in spleen size in multiple SMA mouse models and a pathological reduction in red pulp and extramedullary hematopoiesis. Additionally, red pulp macrophages, a discrete subset of yolk sac-derived macrophages, were found to be altered in SMA spleens even in pre-symptomatic post-natal day 2 animals. These cells, which are involved in iron metabolism and the phagocytosis of erythrocytes and blood-borne pathogens are significantly reduced prior to the development of the neurodegenerative hallmarks of SMA, implying a differential role of SMN in myeloid cell ontogeny. Collectively, these results demonstrate that SMN deficiency impacts spleen development and suggests a potential role for immunological development in SMA.
Topics: Animals; Disease Models, Animal; Embryonic Development; Erythrocytes; Hematopoiesis, Extramedullary; Humans; Inflammation; Iron; Macrophages; Mice; Motor Neurons; Muscular Atrophy, Spinal; Myeloid Cells; Phagocytosis; Spleen; Survival of Motor Neuron 1 Protein
PubMed: 28062667
DOI: 10.1093/hmg/ddx008 -
BioMed Research International 2020Defensins are a class of antimicrobial peptides in vertebrates that function as the first line of innate immunity with potent antimicrobial and immunomodulatory...
Defensins are a class of antimicrobial peptides in vertebrates that function as the first line of innate immunity with potent antimicrobial and immunomodulatory activities. Fourteen defensins, namely, avian -defensin 1 to 14 (-14), have been identified in chickens. Before characterizing the role of s in innate immunity during the early development of chickens, we collected tissue segments from the liver, spleen, and gastrointestinal (GI) tract including the esophagus, crop, proventriculus, gizzard, duodenum, jejunum, ileum, cecum, and colon from broilers at days 1, 3, 7, 14, and 28. After RNA isolation and reverse transcription, we determined the expression levels of the 14 genes in these tissues during the first 28 days after hatching by real-time PCR. The results suggested the s were widely expressed in the chicken liver, spleen, and gastrointestinal (GI) tract. Interestingly, we did not detect expressed in the GI tract, even in the liver and spleen. Additionally, s were differentially expressed in the chicken GI tract. and were expressed most abundantly in the proximal GI tract, especially the esophagus and crop. Moreover, , , , and were expressed in an inverted-V pattern with the peak being the observed expression at days 3, 7, or 14 in the chicken spleen, esophagus, duodenum, and cecum. Other s presented biphasic or inverted-V expression patterns in different tissues. The expression levels of all detected s were strengthened after hatching rather than decreasing steadily. Therefore, s were found to be expressed widely in the chicken liver, spleen, and GI tract and their expression levels were primarily up regulated during the early development of chicken, implying the potential essential roles of s in early innate defense and infection resistance of chickens.
Topics: Aging; Animals; Chickens; Digestive System; Organ Specificity; Real-Time Polymerase Chain Reaction; Spleen; beta-Defensins
PubMed: 33490238
DOI: 10.1155/2020/2567861 -
BMC Genomics Aug 2023Numerous circular RNAs (circRNAs) have been recently identified in porcine tissues and cell types. Nevertheless, their significance in porcine spleen development is yet...
BACKGROUND
Numerous circular RNAs (circRNAs) have been recently identified in porcine tissues and cell types. Nevertheless, their significance in porcine spleen development is yet unelucidated. Herein, we reported an extensive overlook of circRNA expression profile during spleen development in Meishan pigs.
RESULTS
Overall, 39,641 circRNAs were identified from 6,914 host genes. Among them, many circRNAs are up- or down-regulated at different time points of pig spleen development. Using WGCNA analysis, we revealed two essential modules for protein-coding genes and circRNAs. Subsequent correlation analysis revealed 67 circRNAs/co-expressed genes that participated in immnue-associated networks. Furthermore, a competing endogenous RNA (ceRNA) network analysis of circRNAs revealed that 12 circRNAs modulated CD226, MBD2, SAMD3, SIT1, SRP14, SYTL3 gene expressions via acting as miRNA sponges. Moreover, the circRNA_21767/miR-202-3p axis regulated SIT1 expression in a ceRNA manner, which is critical for the immune-based regulation of spleen development in Meishan pigs.
CONCLUSIONS
Overall, our results demonstrated that the circRNAs were differentially expressed during different stages of porcine spleen development, meanwhile the circRNAs interacted with immune-related genes in a ceRNA-based fashion. Moreover, we presented biomedical researchers with RNAseqTools, a user-friendly and powerful software for the visualization of transcriptome profile data.
Topics: Animals; DNA-Binding Proteins; MicroRNAs; RNA, Circular; Spleen; Swine; Genome-Wide Association Study; China
PubMed: 37612620
DOI: 10.1186/s12864-023-09612-x -
Parasites & Vectors Jan 2021Babesia is a protozoan parasite that infects red blood cells in some vertebrates. Some species of Babesia can induce zoonoses and cause considerable harm. As the largest...
BACKGROUND
Babesia is a protozoan parasite that infects red blood cells in some vertebrates. Some species of Babesia can induce zoonoses and cause considerable harm. As the largest immune organ in mammals, the spleen plays an important role in defending against Babesia infection. When infected with Babesia, the spleen is seriously injured but still actively initiates immunomodulatory responses.
METHODS
To explore the molecular mechanisms underlying the immune regulation and self-repair of the spleen in response to infection, this study used data-independent acquisition (DIA) quantitative proteomics to analyse changes in expression levels of global proteins and in phosphorylation modification in spleen tissue after Babesia microti infection in mice.
RESULTS
After mice were infected with B. microti, their spleens were seriously damaged. Using bioinformatics methods to analyse dynamic changes in a large number of proteins, we found that the spleen still initiated immune responses to combat the infection, with immune-related proteins playing an important role, including cathepsin D (CTSD), interferon-induced protein 44 (IFI44), interleukin-2 enhancer-binding factor 2 (ILF2), interleukin enhancer-binding factor 3 (ILF3) and signal transducer and activator of transcription 5A (STAT5A). In addition, some proteins related to iron metabolism were also involved in the repair of the spleen after B. microti infection, including serotransferrin, lactoferrin, transferrin receptor protein 1 (TfR1) and glutamate-cysteine ligase (GCL). At the same time, the expression and phosphorylation of proteins related to the growth and development of the spleen also changed, including protein kinase C-δ (PKC-δ), mitogen-activated protein kinase (MAPK) 3/1, growth factor receptor-bound protein 2 (Grb2) and P21-activated kinase 2 (PAK2).
CONCLUSIONS
Immune-related proteins, iron metabolism-related proteins and growth and development-related proteins play an important role in the regulation of spleen injury and maintenance of homeostasis. This study provides an important basis for the diagnosis and treatment of babesiosis.
Topics: Animals; Babesia microti; Babesiosis; Computational Biology; Female; Gene Expression Regulation; Mice; Mice, Inbred BALB C; Parasitemia; Proteins; Proteomics; Spleen; Transcription Factors
PubMed: 33468223
DOI: 10.1186/s13071-020-04574-5 -
The British Journal of Radiology Apr 2023Adult spleens show extensive morphological variation, with a reported prevalence of 40-98% clefts (also called notches or fissures) on the splenic surface and...
OBJECTIVES
Adult spleens show extensive morphological variation, with a reported prevalence of 40-98% clefts (also called notches or fissures) on the splenic surface and 10-30% accessory spleens at autopsy. It is hypothesised that both anatomical variants result from a complete or partial failure of multiple splenic primordia to fuse to the main body. According to this hypothesis, fusion of the spleen primordia is completed after birth and spleen morphological variations are often explained as stagnation of spleen development at the foetal stage. We tested this hypothesis by studying early spleen development in embryos, and compared foetal and adult spleen morphology.
METHODS AND MATERIALS
We assessed 22 embryonic, 17 foetal and 90 adult spleens on the presence of clefts using histology, micro-CT and conventional post-mortem CT-scans, respectively.
RESULTS
The spleen primordium was observed as a single mesenchymal condensation in all embryonic specimens. The number of clefts varied from 0 to 6 in foetuses, compared to 0-5 in adults. We found no correlation between foetal age and number of clefts (R = 0.004). The independent samples Kolmogorov-Smirnov test showed no significant difference in the total number of clefts between adult and foetal spleens ( = 0.068).
CONCLUSION
We found no morphological evidence for a multifocal origin or a lobulated developmental stage of the human spleen.
ADVANCES IN KNOWLEDGE
Our findings show that splenic morphology is highly variable, independent of developmental stage and age. We suggest to abandon the term "persistent foetal lobulation" and to regard splenic clefts, regardless of their number or location, as normal variants.
Topics: Adult; Humans; Spleen; Autopsy; Gestational Age; X-Ray Microtomography; Anatomic Variation
PubMed: 36802835
DOI: 10.1259/bjr.20220744 -
Malaria Journal Jun 2021Malaria is a fatal disease that presents clinically as a continuum of symptoms and severity, which are determined by complex host-parasite interactions. Clearance of...
BACKGROUND
Malaria is a fatal disease that presents clinically as a continuum of symptoms and severity, which are determined by complex host-parasite interactions. Clearance of infection is believed to be accomplished by the spleen and mononuclear phagocytic system (MPS), independent of artemisinin treatment. The spleen filters infected red blood cells (RBCs) from circulation through immune-mediated recognition of the infected RBCs followed by phagocytosis. This study evaluated the tolerance of four different strains of mice to Plasmodium berghei strain K173 (P. berghei K173), and the differences in the role of the spleen in controlling P. berghei K173 infection.
METHODS
Using different strains of mice (C57BL/6, BALB/C, ICR, and KM mice) infected with P. berghei K173, the mechanisms leading to splenomegaly, histopathology, splenocyte activation and proliferation, and their relationship to the control of parasitaemia and host mortality were examined and evaluated.
RESULTS
Survival time of mice infected with P. berghei K173 varied, although the infection was uniformly lethal. Mice of the C57BL/6 strain were the most resistant, while mice of the strain ICR were the most susceptible. BALB/c and KM mice were intermediate. In the course of P. berghei K173 infection, all infected mice experienced significant splenomegaly. Parasites were observed in the red pulp at 3 days post infection (dpi) in all animals. All spleens retained late trophozoite stages as well as a fraction of earlier ring-stage parasites. The percentages of macrophages in infected C57BL/6 and KM mice were higher than uninfected mice on 8 dpi. Spleens of infected ICR and KM mice exhibited structural disorganization and remodelling. Furthermore, parasitaemia was significantly higher in KM versus C57BL/6 mice at 8 dpi. The percentages of macrophages in ICR infected mice were lower than uninfected mice, and the parasitaemia was higher than other strains.
CONCLUSIONS
The results presented here demonstrate the rate of splenic mechanical filtration and that splenic macrophages are the predominant roles in controlling an individual's total parasite burden. This can influence the pathogenesis of malaria. Finally, different genetic backgrounds of mice have different splenic mechanisms for controlling malaria infection.
Topics: Animals; Hematologic Tests; Malaria; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred ICR; Plasmodium berghei; Spleen; Mice
PubMed: 34090420
DOI: 10.1186/s12936-021-03786-z -
Journal of Pediatric Surgery Jun 2019The purpose of this study is to evaluate splenic effects during artificial placenta (AP) support.
INTRODUCTION
The purpose of this study is to evaluate splenic effects during artificial placenta (AP) support.
METHODS
AP lambs (118-121 d, n = 14) were delivered and placed on the AP support for a goal of 10-14 days. Cannulation used right jugular drainage and umbilical vein reinfusion. Early (ETC; 115-120 d; n = 7) and late (LTC; 125-131 d; n = 7) tissue controls were delivered and immediately sacrificed. Spleens were formalin fixed, H&E stained, and graded for injury, response to inflammation, and extramedullary hematopoiesis (EMH). CD68 and CD163 stains were used to assess for macrophage activation and density. Clinical variables were correlated with splenic scores. Groups were compared using Fisher's Exact Test and descriptive statistics. p < 0.05 indicated significance.
RESULTS
Mean survival for AP lambs was 12 ± 5 d. There was no necrosis found in any of the groups. Vascular congestion and sinusoidal histiocytosis did not significantly differ between AP and control groups (p = 0.72; p = 0.311). There were significantly more pigmented macrophages (p = 0.008), CD163 (p = <0.001), and CD68 (p = <0.001) stained cells in the AP group. ETC and LTC demonstrated more EMH than AP spleens (p = <0.001).
CONCLUSIONS
During AP support, spleens appear to develop normally and exhibit an appropriate inflammatory response. After initiation of AP support, EMH transitions away from the spleen.
STUDY TYPE
Research Paper/Therapeutic Potential.
LEVEL OF EVIDENCE
N/A.
Topics: Animals; Artificial Organs; Female; Placenta; Pregnancy; Premature Birth; Sheep; Sheep, Domestic; Spleen
PubMed: 30902457
DOI: 10.1016/j.jpedsurg.2019.02.041 -
Journal of Virology Jan 2016Infections with Sudan virus (SUDV), a member of the genus Ebolavirus, result in a severe hemorrhagic fever with a fatal outcome in over 50% of human cases. The paucity...
UNLABELLED
Infections with Sudan virus (SUDV), a member of the genus Ebolavirus, result in a severe hemorrhagic fever with a fatal outcome in over 50% of human cases. The paucity of prophylactics and therapeutics against SUDV is attributed to the lack of a small-animal model to screen promising compounds. By repeatedly passaging SUDV within the livers and spleens of guinea pigs in vivo, a guinea pig-adapted SUDV variant (SUDV-GA) uniformly lethal to these animals, with a 50% lethal dose (LD50) of 5.3 × 10(-2) 50% tissue culture infective doses (TCID50), was developed. Animals infected with SUDV-GA developed high viremia and died between 9 and 14 days postinfection. Several hallmarks of SUDV infection, including lymphadenopathy, increased liver enzyme activities, and coagulation abnormalities, were observed. Virological analyses and gross pathology, histopathology, and immunohistochemistry findings indicate that SUDV-GA replicates in the livers and spleens of infected animals similarly to SUDV infections in nonhuman primates. These developments will accelerate the development of specific medical countermeasures in preparation for a future disease outbreak due to SUDV.
IMPORTANCE
A disease outbreak due to Ebola virus (EBOV), suspected to have emerged during December 2013 in Guinea, with over 11,000 dead and 28,000 infected, is finally winding down. Experimental EBOV vaccines and treatments were administered to patients under compassionate circumstances with promising results, and availability of an approved countermeasure appears to be close. However, the same range of experimental candidates against a potential disease outbreak caused by other members of the genus Ebolavirus, such as Sudan virus (SUDV), is not readily available. One bottleneck contributing to this situation is the lack of a small-animal model to screen promising drugs in an efficient and economical manner. To address this, we have generated a SUDV variant (SUDV-GA) that is uniformly lethal to guinea pigs. Animals infected with SUDV-GA develop disease similar to that of SUDV-infected humans and monkeys. We believe that this model will significantly accelerate the development of life-saving measures against SUDV infections.
Topics: Adaptation, Biological; Animals; Disease Models, Animal; Ebolavirus; Guinea Pigs; Hemorrhagic Fever, Ebola; Lethal Dose 50; Liver; Spleen; Survival Analysis
PubMed: 26491156
DOI: 10.1128/JVI.02331-15