scholarly journals Brucella: Reservoirs and Niches in Animals and Humans

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 186 ◽  
Author(s):  
Gabriela González-Espinoza ◽  
Vilma Arce-Gorvel ◽  
Sylvie Mémet ◽  
Jean-Pierre Gorvel
Keyword(s):  
Bone Marrow ◽  
Intracellular Pathogen ◽  
Chronic Infections ◽  
Chronic Complications ◽  
Adipose Tissues ◽  
Wildlife Reservoirs ◽  
Brucella Infection ◽  
Asymptomatic Subjects ◽  
First Time

Brucella is an intracellular bacterium that causes abortion, reproduction failure in livestock and leads to a debilitating flu-like illness with serious chronic complications if untreated in humans. As a successful intracellular pathogen, Brucella has developed strategies to avoid recognition by the immune system of the host and promote its survival and replication. In vivo, Brucellae reside mostly within phagocytes and other cells including trophoblasts, where they establish a preferred replicative niche inside the endoplasmic reticulum. This process is central as it gives Brucella the ability to maintain replicating-surviving cycles for long periods of time, even at low bacterial numbers, in its cellular niches. In this review, we propose that Brucella takes advantage of the environment provided by the cellular niches in which it resides to generate reservoirs and disseminate to other organs. We will discuss how the favored cellular niches for Brucella infection in the host give rise to anatomical reservoirs that may lead to chronic infections or persistence in asymptomatic subjects, and which may be considered as a threat for further contamination. A special emphasis will be put on bone marrow, lymph nodes, reproductive and for the first time adipose tissues, as well as wildlife reservoirs.

scholarly journals A Novel Inhibitory Protein in Adipose Tissue, the Aldo-Keto Reductase AKR1B7: Its Role in Adipogenesis

Endocrinology ◽  
2007 ◽  
Vol 148 (5) ◽  
pp. 1996-2005 ◽  
Author(s):  
Julien Tirard ◽  
Johann Gout ◽  
Anne Marie Lefrançois-Martinez ◽  
Antoine Martinez ◽  
Martine Begeot ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Primary Cultures ◽  
Inhibitory Protein ◽  
Adipose Stromal Cells ◽  
Adipose Tissues ◽  
Detoxification Enzyme ◽  
In Vivo Experiments ◽  
First Time

The aldo-keto reductase 1B7 (AKR1B7) encodes an aldose-reductase that has been reported as a detoxification enzyme until now. We have demonstrated that AKR1B7 is differently expressed in various mouse white adipose tissues depending on their location. Its expression is associated with a higher ratio of preadipocytes vs. adipocytes. The cells that express AKR1B7 did not contain lipid droplets, and the expression level of akr1b7 was very low in mature adipocytes. We have defined the role of AKR1B7 in adipogenesis using either primary cultures of adipose stromal cells (containing adipocyte precursors) or the 3T3-L1 cell line. Under the same differentiation conditions, adipose stromal cells from tissues that expressed AKR1B7 had a decreased capacity to accumulate lipids compared with those that did not express it. Moreover, the overexpression of sense or antisense AKR1B7 in 3T3-L1 preadipocytes inhibited or accelerated, respectively, their rate of differentiation into adipocytes. In vivo experiments demonstrated that AKR1B7-encoding mRNA expression decreased in adipose tissues from mice where obesity was induced by a high-fat diet. All these results attributed for the first time a novel role to AKR1B7, which is the inhibition of adipogenesis in some adipose tissues.

scholarly journals Neutrophil mobilization via plerixafor-mediated CXCR4 inhibition arises from lung demargination and blockade of neutrophil homing to the bone marrow

2013 ◽  
Vol 210 (11) ◽  
pp. 2321-2336 ◽  
Author(s):  
Sapna Devi ◽  
Yilin Wang ◽  
Weng Keong Chew ◽  
Ronald Lima ◽  
Noelia A-González ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Host Defense ◽  
Multiphoton Microscopy ◽  
Blood Neutrophil ◽  
Cxcr4 Antagonist ◽  
Treatment Regimens ◽  
Blood Neutrophils ◽  
Neutropenic Patients ◽  
First Time

Blood neutrophil homeostasis is essential for successful host defense against invading pathogens. Circulating neutrophil counts are positively regulated by CXCR2 signaling and negatively regulated by the CXCR4–CXCL12 axis. In particular, G-CSF, a known CXCR2 signaler, and plerixafor, a CXCR4 antagonist, have both been shown to correct neutropenia in human patients. G-CSF directly induces neutrophil mobilization from the bone marrow (BM) into the blood, but the mechanisms underlying plerixafor-induced neutrophilia remain poorly defined. Using a combination of intravital multiphoton microscopy, genetically modified mice and novel in vivo homing assays, we demonstrate that G-CSF and plerixafor work through distinct mechanisms. In contrast to G-CSF, CXCR4 inhibition via plerixafor does not result in neutrophil mobilization from the BM. Instead, plerixafor augments the frequency of circulating neutrophils through their release from the marginated pool present in the lung, while simultaneously preventing neutrophil return to the BM. Our study demonstrates for the first time that drastic changes in blood neutrophils can originate from alternative reservoirs other than the BM, while implicating a role for CXCR4–CXCL12 interactions in regulating lung neutrophil margination. Collectively, our data provides valuable insights into the fundamental regulation of neutrophil homeostasis, which may lead to the development of improved treatment regimens for neutropenic patients.

scholarly journals Hypoxic culture and in vivo inflammatory environments affect the assumption of pericyte characteristics by human adipose and bone marrow progenitor cells

2011 ◽  
Vol 301 (6) ◽  
pp. C1378-C1388 ◽  
Author(s):  
Peter J. Amos ◽  
Carolyn L. Mulvey ◽  
Scott A. Seaman ◽  
Joseph Walpole ◽  
Katherine E. Degen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Stromal Cells ◽  
Cell Types ◽  
Angiogenic Growth Factors ◽  
Adipose Derived Stromal Cells ◽  
Angiogenic Proteins ◽  
First Time

Previous studies have shown that exposure to a hypoxic in vitro environment increases the secretion of pro-angiogenic growth factors by human adipose-derived stromal cells (hASCs) [Cao Y, et al., Biochem Biophys Res Commun 332: 370–379, 2005; Kokai LE, et al., Plast Reconstr Surg 116: 1453–1460, 2005; Park BS, et al., Biomed Res (Tokyo) 31: 27–34, 2010; Rasmussen JG, et al., Cytotherapy 13: 318–328, 2010; Rehman J, et al., Circulation 109: 1292–1298, 2004]. Previously, it has been demonstrated that hASCs can differentiate into pericytes and promote microvascular stability and maintenance during angiogenesis in vivo (Amos PJ, et al., Stem Cells 26: 2682–2690, 2008; Traktuev DO, et al., Circ Res 102: 77–85, 2008). In this study, we tested the hypotheses that angiogenic induction can be increased and pericyte differentiation decreased by pretreatment of hASCs with hypoxic culture and that hASCs are similar to human bone marrow-derived stromal cells (hBMSCs) in these regards. Our data confirms previous studies showing that hASCs: 1) secrete pro-angiogenic proteins, which are upregulated following culture in hypoxia, and 2) migrate up gradients of PDGF-BB in vitro, while showing for the first time that a rat mesenteric model of angiogenesis induced by 48/80 increases the propensity of both hASCs and hBMSCs to assume perivascular phenotypes following injection. Moreover, culture of both cell types in hypoxia before injection results in a biphasic vascular length density response in this model of inflammation-induced angiogenesis. The effects of hypoxia and inflammation on the phenotype of adult progenitor cells impacts both the therapeutic and the basic science applications of the cell types, as hypoxia and inflammation are common features of natural and pathological vascular compartments in vivo.

Novel Evidence That Murine and Human Mesenchymal Stromal Cells Express Functional Gonadotropic Hormone Receptors, Demonstrating the Involvement of the Pituitary gonadotropin–bone Marrow Axis in Hematopoiesis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1588-1588
Author(s):  
Malwina Suszynska ◽  
Pranesh Gunjal ◽  
Agata Poniewierska-Baran ◽  
Sylwia Borkowska ◽  
Kasia Mierzejewska ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Hormone Receptors ◽  
Human Mscs ◽  
Gonadotropin Receptors ◽  
Gonadotropic Hormone ◽  
Pituitary Gonadotropin ◽  
First Time

Abstract Background: Mesenchymal stromal cells (MSCs) play an important role in bone marrow (BM) by providing a supportive microenvironment for hematopoietic stem/progenitor cells (HSPCs). MSCs are also employed in organ regeneration as a rich source of several paracrine signals that inhibit apoptosis and promote angiogenesis in damaged tissues. As reported in the literature, several mediators, including a growth factor (HGF), a chemokine (SDF-1), bioactive lipids (S1P, C1P), and extracellular nucleotides (ATP, UTP), affect MSC biology and migration. In parallel, evidence has accumulated that the most primitive mesodermal precursors of MSCs (small BM-residing and peripheral blood (PB)-circulating Sca-1+Lin–CD45– cells in mice and CD133+Lin–CD45– cells in humans) express certain embryonic stem cell markers, such as the transcription factor Oct-4 and the SSEA-1/4 antigens (Stem Cells Dev. 2014;23:689-701), and also express several genes characteristic of migrating primordial germ cells (Leukemia 2010; 24:1450–1461). Hypothesis: Pursuing observations that most primitive human and murine precursors of MSCs express several germline markers, we became interested in whether murine and human MSCs also express gonadotropic hormone receptors, such as receptors for follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL), and whether these receptors are functional. Materials and Methods: Murine and human MSCs were expanded from a population of adherent murine BM or human umbilical cord blood cells, and cells with low passage numbers were employed for analysis. The expression of gonadotropic receptors (FSH-R, LH-R, and PRL-R) was evaluated by RT-PCR, and the functionality of these receptors was tested in assays for proliferation, chemotaxis, adhesion, and phosphorylation of MAPKp42/44 and AKT. In addition, we also evaluated the expression of gonadotropin receptors by purified murine SKL cells and human CD34+ cells. Results. We report here for the first time that both human and murine MSCs and HSPCs express functional gonadotropin receptors. We found that FSH strongly enhanced proliferation of MSCs in vitro as well as expanded the number of these cells in murine BM after prolonged administration in vivo. We found that all these hormones stimulated chemotaxis and adhesion of murine and human MSCs. These functional responses were correlated with phosphorylation of MAPKp42/44 and AKT. At the same time, we observed that pituitary gonadotropin receptors are expressed by murine and human HSPCs and that these hormones stimulate proliferation and expansion of these cells in vivo in BM as well as in clonogeneic assays in vitro if added along with suboptimal doses of colony-stimulating growth factors. Of note, we did not observe significant differences in the effects of FSH, LH, and PRL between male and female cells. Conclusions. We provide for the first time evidence for the existence of a functional pituitary gonadotropin–hematopoiesis signaling axis, which has important implications for hematopoiesis in young individuals, and we will present gene-array data on changes in gene expression in MSCs after stimulation with gonadotropins. Moreover, since the levels of FSH and LH increase in response to a decrease in gonadal function with advanced age, elevated levels of FSH and LH may affect hematopoiesis and may be factors contributing to the development of leukemia. The stimulatory effect of pituitary gonadotropins on MSCs and HSPCs could also be exploited in the clinic in selected cases as a means to enhance hematopoiesis. Disclosures No relevant conflicts of interest to declare.

Erythropoietin mRNA Expression in Human Fetal and Neonatal Tissue

Blood ◽  
1998 ◽  
Vol 92 (9) ◽  
pp. 3218-3225 ◽  
Author(s):  
Christof Dame ◽  
Hubert Fahnenstich ◽  
Patricia Freitag ◽  
Dietmar Hofmann ◽  
Thair Abdul-Nour ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mrna Expression ◽  
Animal Experiments ◽  
Human Spleen ◽  
Tissue Samples ◽  
Mrna Content ◽  
Total Body ◽  
American Society ◽  
First Time

Abstract Based on animal experiments, a switch of the erythropoietin (EPO) production site from the liver in the fetus to the kidneys in the adult has been postulated. To study the switch in humans, we have quantitated EPO mRNA expression in liver, kidney, spleen, and bone marrow of human fetuses and neonates by means of a competitive polymerase chain reaction (PCR). Tissue samples from 66 routine postmortem examinations were obtained. EPO mRNA was expressed in 97% of the tissue specimen derived from the liver (n = 66) and in 93% of those from the kidneys (17 weeks of gestation until 18 months after birth; n = 59). For the first time the EPO gene was found expressed in vivo in human spleen (96% of 64 samples) and in fetal and neonatal bone marrow (81% of 21 samples). EPO mRNA expression in the kidneys increased significantly beyond 30 weeks of gestation (P < .05). Although there was a slight decrease in EPO mRNA content per g liver tissue towards birth, the liver accounted for about 80% of the total body EPO mRNA. The contribution of the spleen and bone marrow were minor compared with liver and kidneys. Our results indicate that in humans the liver is the primary site of EPO gene expression not only in fetal, but also in neonatal life. A significant increase of renal EPO mRNA expression after 30 weeks of gestation might indicate the beginning switch. © 1998 by The American Society of Hematology.

scholarly journals Platelet-derived extracellular vesicles infiltrate and modify the bone marrow during inflammation

2020 ◽  
Vol 4 (13) ◽  
pp. 3011-3023 ◽  
Author(s):  
Shauna L. French ◽  
Kirill R. Butov ◽  
Isabelle Allaeys ◽  
Jorge Canas ◽  
Golnaz Morad ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Extracellular Vesicles ◽  
Target Cells ◽  
Wild Type ◽  
Plasma Factors ◽  
First Time ◽  
Novel Model

Abstract During inflammation, steady-state hematopoiesis switches to emergency hematopoiesis to repopulate myeloid cells, with a bias toward the megakaryocytic lineage. Soluble inflammatory cues are thought to be largely responsible for these alterations. However, how these plasma factors rapidly alter the bone marrow (BM) is not understood. Inflammation also drives platelet activation, causing the release of platelet-derived extracellular vesicles (PEVs), which package diverse cargo and reprogram target cells. We hypothesized that PEVs infiltrate the BM, providing a direct mode of communication between the plasma and BM environments. We transfused fluorescent, wild-type (MPL+) platelets into recipient cMpl−/−mice before triggering systemic inflammation. Twenty hours postinfusion, we observed significant infiltration of donor platelet-derived particles in the BM, which we tracked immunophenotypically (MPL+ immunohistochemistry staining) and quantified by flow cytometry. To determine if this phenomenon relates to humans, we extensively characterized both megakaryocyte-derived and PEVs generated in vitro and in vivo, and found enrichment of extracellular vesicles in bone marrow compared with autologous peripheral blood. Last, BM from cMpl−/− mice was cultured in the presence or absence of wild-type (MPL+) PEVs. After 72 hours, flow cytometry revealed increased megakaryocytes only in cultures with added PEVs. The majority of CD41+ cells were bound to PEVs, suggesting a PEV-mediated rescue of megakaryopoiesis. In conclusion, we report for the first time that plasma-residing PEVs infiltrate the BM. Further, PEVs interact with BM cells in vivo and in vitro, causing functional reprogramming that may represent a novel model of inflammation-induced hematopoiesis.

Erythropoietin mRNA Expression in Human Fetal and Neonatal Tissue

Blood ◽  
1998 ◽  
Vol 92 (9) ◽  
pp. 3218-3225 ◽  
Author(s):  
Christof Dame ◽  
Hubert Fahnenstich ◽  
Patricia Freitag ◽  
Dietmar Hofmann ◽  
Thair Abdul-Nour ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mrna Expression ◽  
Animal Experiments ◽  
Human Spleen ◽  
Tissue Samples ◽  
Mrna Content ◽  
Total Body ◽  
American Society ◽  
First Time

Based on animal experiments, a switch of the erythropoietin (EPO) production site from the liver in the fetus to the kidneys in the adult has been postulated. To study the switch in humans, we have quantitated EPO mRNA expression in liver, kidney, spleen, and bone marrow of human fetuses and neonates by means of a competitive polymerase chain reaction (PCR). Tissue samples from 66 routine postmortem examinations were obtained. EPO mRNA was expressed in 97% of the tissue specimen derived from the liver (n = 66) and in 93% of those from the kidneys (17 weeks of gestation until 18 months after birth; n = 59). For the first time the EPO gene was found expressed in vivo in human spleen (96% of 64 samples) and in fetal and neonatal bone marrow (81% of 21 samples). EPO mRNA expression in the kidneys increased significantly beyond 30 weeks of gestation (P < .05). Although there was a slight decrease in EPO mRNA content per g liver tissue towards birth, the liver accounted for about 80% of the total body EPO mRNA. The contribution of the spleen and bone marrow were minor compared with liver and kidneys. Our results indicate that in humans the liver is the primary site of EPO gene expression not only in fetal, but also in neonatal life. A significant increase of renal EPO mRNA expression after 30 weeks of gestation might indicate the beginning switch. © 1998 by The American Society of Hematology.

scholarly journals Preclinical models of human multiple myeloma subgroups

2021 ◽  
Author(s):  
Wiebke Winkler ◽  
Carlota Farré Díaz ◽  
Eric Blanc ◽  
Hanna Napieczynska ◽  
Patrick Langner ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Germinal Center ◽  
Plasma Cells ◽  
Bone Lesions ◽  
Preclinical Models ◽  
Co Activation ◽  
Human Multiple Myeloma ◽  
First Time

Multiple myeloma (MM), a tumor of germinal center (GC)-experienced plasma cells, comprises distinct genetic subgroups, such as the t(11;14)/CCND1 and the t(4;14)/MMSET subtype. We have generated subgroup-specific MM models by the GC B cell-specific co-activation of Ccnd1 or MMSET with a constitutively active Ikk2 mutant, mimicking the secondary NFκB activation frequently seen in human MM. Ccnd1/Ikk2ca and MMSET/Ikk2ca mice developed a pronounced, clonally restricted plasma cell outgrowth with age, accompanied by serum M spikes, bone marrow insufficiency and bone lesions. The transgenic plasma cells could be propagated in vivo and showed transcriptional profiles resembling their human counterparts. Thus, we show that Ccnd1 and MMSET cooperate with NFκB in MM pathogenesis, considering for the first time the genetic heterogeneity of MM for the generation of preclinical models.

Sinusoidal Cells in Bone Marrow Take Up BSA-Au Conjugates in the Presence of an Artificial Blood Substitute

1985 ◽  
Vol 43 ◽  
pp. 700-701
Author(s):  
J.S. Geoffroy ◽  
R.P. Becker
Keyword(s):  
Bone Marrow ◽  
Los Angeles ◽  
Iliac Artery ◽  
Blood Substitute ◽  
Sprague Dawley ◽  
Coated Pits ◽  
Sinusoidal Cells ◽  
Artificial Blood ◽  
Left Common Iliac Artery

The pattern of BSA-Au uptake in vivo by endothelial cells of the venous sinuses (sinusoidal cells) of rat bone marrow has been described previously. BSA-Au conjugates are taken up exclusively in coated pits and vesicles, enter and pass through an “endosomal” compartment comprised of smooth-membraned tubules and vacuoles and cup-like bodies, and subsequently reside in multivesicular and dense bodies. The process is very rapid, with BSA-Au reaching secondary lysosmes one minute after presentation. (Figure 1)In further investigations of this process an isolated limb perfusion method using an artificial blood substitute, Oxypherol-ET (O-ET; Alpha Therapeutics, Los Angeles, CA) was developed. Under nembutal anesthesia, male Sprague-Dawley rats were laparotomized. The left common iliac artery and vein were ligated and the right iliac artery was cannulated via the aorta with a small vein catheter. Pump tubing, preprimed with oxygenated 0-ET at 37°C, was connected to the cannula.

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