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Article ; Online: Combination of CD49b and CD229 Reveals a Subset of Multipotent Progenitors With Short-Term Activity Within the Hematopoietic Stem Cell Compartment.

Somuncular, Ece / Su, Tsu-Yi / Dumral, Özge / Johansson, Anne-Sofie / Luc, Sidinh

2023 Volume 12, Issue 11, Page(s) 720–726

Abstract: Hematopoiesis is maintained by hematopoietic stem cells (HSCs) that replenish all blood lineages throughout life. It is well-established that the HSC pool is functionally heterogeneous consisting of cells differing in longevity, self-renewal ability, ... ...

Abstract	Hematopoiesis is maintained by hematopoietic stem cells (HSCs) that replenish all blood lineages throughout life. It is well-established that the HSC pool is functionally heterogeneous consisting of cells differing in longevity, self-renewal ability, cell proliferation, and lineage differentiation. Although HSCs can be identified through the Lineage-Sca-1+c-Kit+CD48-CD34-CD150+ immunophenotype, the cell surface marker combination does not permit absolute purification of functional HSCs with long-term reconstituting ability. Therefore, prospective isolation of long-term HSCs is crucial for mechanistic understanding of the biological functions of HSCs and for resolving functional heterogeneity within the HSC population. Here, we show that the combination of CD229 and CD49b cell surface markers within the phenotypic HSC compartment identifies a subset of multipotent progenitor (MPP) cells with high proliferative activity and short-term reconstituting ability. Thus, the addition of CD229 and CD49b to conventional HSC markers permits prospective isolation of functional HSCs by distinguishing MPPs in the HSC compartment.
MeSH term(s)	Animals ; Mice ; Integrin alpha2/metabolism ; Hematopoietic Stem Cells/metabolism ; Multipotent Stem Cells ; Cell Differentiation ; Hematopoiesis ; Mice, Inbred C57BL
Chemical Substances	Integrin alpha2
Language	English
Publishing date	2023-09-14
Publishing country	England
Document type	Journal Article
ZDB-ID	2642270-0
ISSN	2157-6580 ; 2157-6580
ISSN (online)	2157-6580
ISSN	2157-6580
DOI	10.1093/stcltm/szad057
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Article ; Online: Skin mesenchymal niches maintain and protect AML-initiating stem cells.

Sandhow, Lakshmi / Cai, Huan / Leonard, Elory / Xiao, Pingnan / Tomaipitinca, Luana / Månsson, Alma / Kondo, Makoto / Sun, Xiaoyan / Johansson, Anne-Sofie / Tryggvason, Karl / Kasper, Maria / Järås, Marcus / Qian, Hong

The Journal of experimental medicine

2023 Volume 220, Issue 10

Abstract: Leukemia cutis or leukemic cell infiltration in skin is one of the common extramedullary manifestations of acute myeloid leukemia (AML) and signifies a poorer prognosis. However, its pathogenesis and maintenance remain understudied. Here, we report ... ...

Abstract	Leukemia cutis or leukemic cell infiltration in skin is one of the common extramedullary manifestations of acute myeloid leukemia (AML) and signifies a poorer prognosis. However, its pathogenesis and maintenance remain understudied. Here, we report massive AML cell infiltration in the skin in a transplantation-induced MLL-AF9 AML mouse model. These AML cells could regenerate AML after transplantation. Prospective niche characterization revealed that skin harbored mesenchymal progenitor cells (MPCs) with a similar phenotype as BM mesenchymal stem cells. These skin MPCs protected AML-initiating stem cells (LSCs) from chemotherapy in vitro partially via mitochondrial transfer. Furthermore, Lama4 deletion in skin MPCs promoted AML LSC proliferation and chemoresistance. Importantly, more chemoresistant AML LSCs appeared to be retained in Lama4-/- mouse skin after cytarabine treatment. Our study reveals the characteristics and previously unrecognized roles of skin mesenchymal niches in maintaining and protecting AML LSCs during chemotherapy, meriting future exploration of their impact on AML relapse.
MeSH term(s)	Animals ; Mice ; Prospective Studies ; Stem Cells ; Skin ; Leukemia, Myeloid, Acute ; Mesenchymal Stem Cells
Language	English
Publishing date	2023-07-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218343-2
ISSN	1540-9538 ; 0022-1007
ISSN (online)	1540-9538
ISSN	0022-1007
DOI	10.1084/jem.20220953
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Ua VI Zs.107: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Altered circadian clock gene expression in patients with schizophrenia.

Johansson, Anne-Sofie / Owe-Larsson, Björn / Hetta, Jerker / Lundkvist, Gabriella B

Schizophrenia research

2016 Volume 174, Issue 1-3, Page(s) 17–23

Abstract: Impaired circadian rhythmicity has been reported in several psychiatric disorders. Schizophrenia is commonly associated with aberrant sleep-wake cycles and insomnia. It is not known if schizophrenia is associated with disturbances in molecular ... ...

Abstract	Impaired circadian rhythmicity has been reported in several psychiatric disorders. Schizophrenia is commonly associated with aberrant sleep-wake cycles and insomnia. It is not known if schizophrenia is associated with disturbances in molecular rhythmicity. We cultured fibroblasts from skin samples obtained from patients with chronic schizophrenia and from healthy controls, respectively, and analyzed the circadian expression during 48h of the clock genes CLOCK, BMAL1, PER1, PER2, CRY1, CRY2, REV-ERBα and DBP. In fibroblasts obtained from patients with chronic schizophrenia, we found a loss of rhythmic expression of CRY1 and PER2 compared to cells from healthy controls. We also estimated the sleep quality in these patients and found that most of them suffered from poor sleep in comparison with the healthy controls. In another patient sample, we analyzed mononuclear blood cells from patients with schizophrenia experiencing their first episode of psychosis, and found decreased expression of CLOCK, PER2 and CRY1 compared to blood cells from healthy controls. These novel findings show disturbances in the molecular clock in schizophrenia and have important implications in our understanding of the aberrant rhythms reported in this disease.
Language	English
Publishing date	2016-07
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	639422-x
ISSN	1573-2509 ; 0920-9964
ISSN (online)	1573-2509
ISSN	0920-9964
DOI	10.1016/j.schres.2016.04.029
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Zs.A 2351: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 543: Show issues

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Article ; Online: CD49b identifies functionally and epigenetically distinct subsets of lineage-biased hematopoietic stem cells.

Somuncular, Ece / Hauenstein, Julia / Khalkar, Prajakta / Johansson, Anne-Sofie / Dumral, Özge / Frengen, Nicolai S / Gustafsson, Charlotte / Mocci, Giuseppe / Su, Tsu-Yi / Brouwer, Hugo / Trautmann, Christine L / Vanlandewijck, Michael / Orkin, Stuart H / Månsson, Robert / Luc, Sidinh

Stem cell reports

2022 Volume 17, Issue 7, Page(s) 1546–1560

Abstract: Hematopoiesis is maintained by functionally diverse lineage-biased hematopoietic stem cells (HSCs). The functional significance of HSC heterogeneity and the regulatory mechanisms underlying lineage bias are not well understood. However, absolute ... ...

Abstract	Hematopoiesis is maintained by functionally diverse lineage-biased hematopoietic stem cells (HSCs). The functional significance of HSC heterogeneity and the regulatory mechanisms underlying lineage bias are not well understood. However, absolute purification of HSC subtypes with a pre-determined behavior remains challenging, highlighting the importance of continued efforts toward prospective isolation of homogeneous HSC subsets. In this study, we demonstrate that CD49b subdivides the most primitive HSC compartment into functionally distinct subtypes: CD49b
MeSH term(s)	Cell Differentiation/genetics ; Cell Lineage/genetics ; Hematopoiesis/genetics ; Hematopoietic Stem Cells ; Integrin alpha2 ; Multipotent Stem Cells
Chemical Substances	Integrin alpha2
Language	English
Publishing date	2022-06-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2720528-9
ISSN	2213-6711 ; 2213-6711
ISSN (online)	2213-6711
ISSN	2213-6711
DOI	10.1016/j.stemcr.2022.05.014
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Article ; Online: Ethyl pyruvate modulates adhesive and secretory reactions in human lung epithelial cells.

Johansson, Anne-Sofie / Palmblad, Jan

Life sciences

2009 Volume 84, Issue 23-24, Page(s) 805–809

Abstract: Aims: Ethyl pyruvate (EtP) may prolong survival and ameliorate organ dysfunction in a variety of models of critical illness, e.g. severe sepsis and acute respiratory syndrome, by modulation of the expression of inflammatory mediators. Here, we studied ... ...

Abstract	Aims: Ethyl pyruvate (EtP) may prolong survival and ameliorate organ dysfunction in a variety of models of critical illness, e.g. severe sepsis and acute respiratory syndrome, by modulation of the expression of inflammatory mediators. Here, we studied the effects of EtP on the reactions in and between human neutrophils and lung epithelial (A549) cells in vitro. Main methods: Neutrophil adhesion to, surface expression of ICAM-1 and VCAM-1 on, and release of IL-8 and G-CSF from A549 cells were measured by ELISA after stimulation with IL-1 beta or TNFalpha. Key findings: After treatment of A549 cells with EtP, a substantial reduction in the cytokine-induced adhesion of neutrophils to monolayers was noted, whereas sodium pyruvate (NaP) conferred no reduction. Likewise, treatment with 2.5-10 mM EtP (but not NaP) reduced ICAM-1 and VCAM-1 expression in a dose-dependent fashion. The generation of cytokines of significance for adhesive and proliferative events in host defense, IL-8 and G-CSF, was also potently impaired by EtP. Significance: Exposure of lung epithelial cells to 2.5-10 mM EtP inhibited the generation of inflammatory-regulating cytokines IL-8 and G-CSF, reduced ICAM-1 and VCAM-1 expression and impeded the adhesiveness of neutrophils to lung epithelial cells. These are reactions of significance for early inflammatory responses in the lung, suggesting a role for EtP as a treatment for acute pulmonary conditions.
MeSH term(s)	Cell Adhesion/drug effects ; Cell Adhesion/physiology ; Cell Line, Tumor ; Epithelial Cells/drug effects ; Epithelial Cells/secretion ; Granulocyte Colony-Stimulating Factor/antagonists & inhibitors ; Granulocyte Colony-Stimulating Factor/secretion ; Humans ; Intercellular Adhesion Molecule-1/biosynthesis ; Interleukin-1beta/antagonists & inhibitors ; Interleukin-1beta/physiology ; Interleukin-8/antagonists & inhibitors ; Interleukin-8/secretion ; Lung/cytology ; Lung/drug effects ; Lung/secretion ; Neutrophils/drug effects ; Neutrophils/secretion ; Pyruvates/pharmacology ; Respiratory Mucosa/cytology ; Respiratory Mucosa/drug effects ; Respiratory Mucosa/secretion ; Tumor Necrosis Factor-alpha/antagonists & inhibitors ; Tumor Necrosis Factor-alpha/physiology ; Vascular Cell Adhesion Molecule-1/biosynthesis
Chemical Substances	Interleukin-1beta ; Interleukin-8 ; Pyruvates ; Tumor Necrosis Factor-alpha ; Vascular Cell Adhesion Molecule-1 ; ethyl pyruvate (03O98E01OB) ; Intercellular Adhesion Molecule-1 (126547-89-5) ; Granulocyte Colony-Stimulating Factor (143011-72-7)
Language	English
Publishing date	2009-06-05
Publishing country	Netherlands
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2009.03.012
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Article ; Online: Critical role of Lama4 for hematopoiesis regeneration and acute myeloid leukemia progression.

Cai, Huan / Kondo, Makoto / Sandhow, Lakshmi / Xiao, Pingnan / Johansson, Anne-Sofie / Sasaki, Takako / Zawacka-Pankau, Joanna / Tryggvason, Karl / Ungerstedt, Johanna / Walfridsson, Julian / Ekblom, Marja / Qian, Hong

Blood

2021 Volume 139, Issue 20, Page(s) 3040–3057

Abstract: Impairment of normal hematopoiesis and leukemia progression are 2 well-linked processes during leukemia development and are controlled by the bone marrow (BM) niche. Extracellular matrix proteins, including laminin, are important BM niche components. ... ...

Abstract	Impairment of normal hematopoiesis and leukemia progression are 2 well-linked processes during leukemia development and are controlled by the bone marrow (BM) niche. Extracellular matrix proteins, including laminin, are important BM niche components. However, their role in hematopoiesis regeneration and leukemia is unknown. Laminin α4 (Lama4), a major receptor-binding chain of several laminins, is altered in BM niches in mice with acute myeloid leukemia (AML). So far, the impact of Lama4 on leukemia progression remains unknown. We here report that Lama4 deletion in mice resulted in impaired hematopoiesis regeneration following irradiation-induced stress, which is accompanied by altered BM niche composition and inflammation. Importantly, in a transplantation-induced MLL-AF9 AML mouse model, we demonstrate accelerated AML progression and relapse in Lama4-/- mice. Upon AML exposure, Lama4-/- mesenchymal stem cells (MSCs) exhibited dramatic molecular alterations, including upregulation of inflammatory cytokines that favor AML growth. Lama4-/- MSCs displayed increased antioxidant activities and promoted AML stem cell proliferation and chemoresistance to cytarabine, which was accompanied by increased mitochondrial transfer from the MSCs to AML cells and reduced reactive oxygen species in AML cells in vitro. Similarly, we detected lower levels of reactive oxygen species in AML cells from Lama4-/- mice post-cytarabine treatment. Notably, LAMA4 inhibition or knockdown in human MSCs promoted human AML cell proliferation and chemoprotection. Together, our study for the first time demonstrates the critical role of Lama4 in impeding AML progression and chemoresistance. Targeting Lama4 signaling pathways may offer potential new therapeutic options for AML.
MeSH term(s)	Animals ; Cytarabine/therapeutic use ; Drug Resistance, Neoplasm ; Hematopoiesis/genetics ; Humans ; Laminin/genetics ; Leukemia, Myeloid, Acute/drug therapy ; Mesenchymal Stem Cells ; Mice ; Mice, Knockout ; Reactive Oxygen Species
Chemical Substances	Lama4 protein, mouse ; Laminin ; Reactive Oxygen Species ; Cytarabine (04079A1RDZ)
Language	English
Publishing date	2021-12-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2021011510
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Uh III Zs.140: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Commonly used leukotriene B4 receptor antagonists possess intrinsic activity as agonists in human endothelial cells: Effects on calcium transients, adhesive events and mediator release.

Johansson, Anne-Sofie / Haeggström, Jesper Z / Palmblad, Jan

Prostaglandins, leukotrienes, and essential fatty acids

2011 Volume 84, Issue 3-4, Page(s) 109–112

Abstract: Leukotriene B4 (LTB4), a potent chemotactic and immune-modulating lipid mediator, signals via two receptors, BLT1 and BLT2, leading to pro-inflammatory responses in phagocytes. Recently, we reported that BLT1 is the predominating BLT on human umbilical ... ...

Abstract	Leukotriene B4 (LTB4), a potent chemotactic and immune-modulating lipid mediator, signals via two receptors, BLT1 and BLT2, leading to pro-inflammatory responses in phagocytes. Recently, we reported that BLT1 is the predominating BLT on human umbilical vein endothelial cells (HUVEC) and transmits a variety of functional responses. Here, we demonstrate that, in HUVEC, two BLT1 antagonists (U75302, CP105696) and one BLT2 antagonist (LY255283) possess intrinsic but varying agonist activity for adhesion of neutrophils, up-regulation of E-selectin, ICAM-1 and VCAM-1, and release of MCP-1. These effects were observed after exposure of HUVEC for the drugs for 0.25-6h, persisted for several hours, and were less potent in magnitude as those elicited by LPS. Our findings may have consequences for interpretation of in vitro BLT blockade experiments.
MeSH term(s)	Benzopyrans/pharmacology ; Calcium/metabolism ; Carboxylic Acids/pharmacology ; Cell Adhesion/drug effects ; Chemokine CCL2/metabolism ; E-Selectin/genetics ; E-Selectin/metabolism ; Endothelial Cells/drug effects ; Endothelial Cells/metabolism ; Fatty Alcohols/pharmacology ; Glycols/pharmacology ; Humans ; Intercellular Adhesion Molecule-1/genetics ; Intercellular Adhesion Molecule-1/metabolism ; Leukotriene Antagonists/pharmacology ; Neutrophils/metabolism ; Receptors, Leukotriene B4/antagonists & inhibitors ; Tetrazoles/pharmacology ; Up-Regulation ; Vascular Cell Adhesion Molecule-1/genetics ; Vascular Cell Adhesion Molecule-1/metabolism
Chemical Substances	Benzopyrans ; CCL2 protein, human ; Carboxylic Acids ; Chemokine CCL2 ; E-Selectin ; Fatty Alcohols ; Glycols ; LTB4R protein, human ; Leukotriene Antagonists ; Receptors, Leukotriene B4 ; Tetrazoles ; Vascular Cell Adhesion Molecule-1 ; U 75302 (119477-85-9) ; Intercellular Adhesion Molecule-1 (126547-89-5) ; LY 255283 (H037W1I5AL) ; Calcium (SY7Q814VUP) ; CP 105696 (Z7354TW4BM)
Language	English
Publishing date	2011-03
Publishing country	Scotland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	286714-x
ISSN	1532-2823 ; 0952-3278
ISSN (online)	1532-2823
ISSN	0952-3278
DOI	10.1016/j.plefa.2010.11.003
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Article ; Online: A genetic CLOCK variant associated with cluster headache causing increased mRNA levels.

Fourier, Carmen / Ran, Caroline / Zinnegger, Margret / Johansson, Anne-Sofie / Sjöstrand, Christina / Waldenlind, Elisabet / Steinberg, Anna / Belin, Andrea Carmine

Cephalalgia : an international journal of headache

2017 Volume 38, Issue 3, Page(s) 496–502

Abstract: Background Cluster headache is characterized by recurrent unilateral headache attacks of severe intensity. One of the main features in a majority of patients is a striking rhythmicity of attacks. The CLOCK ( Circadian Locomotor Output Cycles Kaput) gene ... ...

Abstract	Background Cluster headache is characterized by recurrent unilateral headache attacks of severe intensity. One of the main features in a majority of patients is a striking rhythmicity of attacks. The CLOCK ( Circadian Locomotor Output Cycles Kaput) gene encodes a transcription factor that serves as a basic driving force for circadian rhythm in humans and is therefore particularly interesting as a candidate gene for cluster headache. Methods We performed an association study on a large Swedish cluster headache case-control sample (449 patients and 677 controls) screening for three single nucleotide polymorphisms (SNPs) in the CLOCK gene implicated in diurnal preference (rs1801260) or sleep duration (rs11932595 and rs12649507), respectively. We further wanted to investigate the effect of identified associated SNPs on CLOCK gene expression. Results We found a significant association with rs12649507 and cluster headache ( p = 0.0069) and this data was strengthened when stratifying for reported diurnal rhythmicity of attacks ( p = 0.0009). We investigated the effect of rs12649507 on CLOCK gene expression in human primary fibroblast cultures and identified a significant increase in CLOCK mRNA expression ( p = 0.0232). Conclusions Our results strengthen the hypothesis of the involvement of circadian rhythm in cluster headache.
MeSH term(s)	Adult ; Aged ; CLOCK Proteins/genetics ; Case-Control Studies ; Cluster Headache/genetics ; Female ; Genetic Predisposition to Disease/genetics ; Genome-Wide Association Study ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; RNA, Messenger/metabolism
Chemical Substances	RNA, Messenger ; CLOCK Proteins (EC 2.3.1.48) ; CLOCK protein, human (EC 2.3.1.48)
Language	English
Publishing date	2017-03-09
Publishing country	England
Document type	Journal Article
ZDB-ID	604567-4
ISSN	1468-2982 ; 0333-1024
ISSN (online)	1468-2982
ISSN	0333-1024
DOI	10.1177/0333102417698709
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Article ; Online: Characterization of the bone marrow niche in patients with chronic myeloid leukemia identifies CXCL14 as a new therapeutic option.

Dolinska, Monika / Cai, Huan / Månsson, Alma / Shen, Jingyi / Xiao, Pingnan / Bouderlique, Thibault / Li, Xidan / Leonard, Elory / Chang, Marcus / Gao, Yuchen / Medina, Juan Pablo / Kondo, Makoto / Sandhow, Lakshmi / Johansson, Anne-Sofie / Deneberg, Stefan / Söderlund, Stina / Jädersten, Martin / Ungerstedt, Johanna / Tobiasson, Magnus /

Östman, Arne / Mustjoki, Satu / Stenke, Leif / Le Blanc, Katarina / Hellström-Lindberg, Eva / Lehmann, Sören / Ekblom, Marja / Olsson-Strömberg, Ulla / Sigvardsson, Mikael / Qian, Hong

Blood

2023 Volume 142, Issue 1, Page(s) 73–89

Abstract: Although tyrosine kinase inhibitors (TKIs) are effective in treating chronic myeloid leukemia (CML), they often fail to eradicate the leukemia-initiating stem cells (LSCs), causing disease persistence and relapse. Evidence indicates that LSC persistence ... ...

Abstract	Although tyrosine kinase inhibitors (TKIs) are effective in treating chronic myeloid leukemia (CML), they often fail to eradicate the leukemia-initiating stem cells (LSCs), causing disease persistence and relapse. Evidence indicates that LSC persistence may be because of bone marrow (BM) niche protection; however, little is known about the underlying mechanisms. Herein, we molecularly and functionally characterize BM niches in patients with CML at diagnosis and reveal the altered niche composition and function in these patients. Long-term culture initiating cell assay showed that the mesenchymal stem cells from patients with CML displayed an enhanced supporting capacity for normal and CML BM CD34+CD38- cells. Molecularly, RNA sequencing detected dysregulated cytokine and growth factor expression in the BM cellular niches of patients with CML. Among them, CXCL14 was lost in the BM cellular niches in contrast to its expression in healthy BM. Restoring CXCL14 significantly inhibited CML LSC maintenance and enhanced their response to imatinib in vitro, and CML engraftment in vivo in NSG-SGM3 mice. Importantly, CXCL14 treatment dramatically inhibited CML engraftment in patient-derived xenografted NSG-SGM3 mice, even to a greater degree than imatinib, and this inhibition persisted in patients with suboptimal TKI response. Mechanistically, CXCL14 upregulated inflammatory cytokine signaling but downregulated mTOR signaling and oxidative phosphorylation in CML LSCs. Together, we have discovered a suppressive role of CXCL14 in CML LSC growth. CXCL14 might offer a treatment option targeting CML LSCs.
MeSH term(s)	Animals ; Mice ; Bone Marrow/metabolism ; Chemokines, CXC/metabolism ; Chemokines, CXC/pharmacology ; Chemokines, CXC/therapeutic use ; Cytokines/metabolism ; Imatinib Mesylate/pharmacology ; Imatinib Mesylate/therapeutic use ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism ; Neoplastic Stem Cells/metabolism ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Signal Transduction
Chemical Substances	Chemokines, CXC ; CXCL14 protein, mouse ; Cytokines ; Imatinib Mesylate (8A1O1M485B) ; Protein Kinase Inhibitors ; CXCL14 protein, human
Language	English
Publishing date	2023-01-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2022016896
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Article ; Online: Subcellular localization of leukotriene receptors in human endothelial cells.

Johansson, Anne-Sofie / Haeggström, Jesper Z / Hultenby, Kjell / Palmblad, Jan

Experimental cell research

2010 Volume 316, Issue 17, Page(s) 2790–2796

Abstract: Leukotriene B(4) (LTB(4)), a potent chemotactic and immune-modulating mediator, signals via two receptors, BLT(1) and BLT(2). Recently, we reported that BLT(1) is the predominating BLT expressed on human umbilical vein endothelial cells (HUVEC), and that ...

Abstract	Leukotriene B(4) (LTB(4)), a potent chemotactic and immune-modulating mediator, signals via two receptors, BLT(1) and BLT(2). Recently, we reported that BLT(1) is the predominating BLT expressed on human umbilical vein endothelial cells (HUVEC), and that BLT(1) mediated functions are enhanced by LTB(4) and lipopolysaccharide (LPS), but not by TNFα. Here, we demonstrate that BLT(1) is found on the outer cell membrane of HUVECs but also in intracellular granules, co-localized with monocyte chemotactic protein-1 and P-selectin, but not with interleukin-8 and von Willebrand factor. Upon stimulation with LTB(4) or LPS, more BLT(1) protein is found, now evenly distributed over the cytoplasm and in the cell nucleus, but less on the cell surface. An MAP kinase inhibitor prevented this enhancement and translocation, suggesting this signaling pathway to be crucial. Thus, BLT(1), a G-protein-coupled 7-transmembrane receptor, is located in various subcellular compartments in endothelial cells, which may have implications for cellular LT dependent responses and target accessibility for BLT(1) antagonists.
MeSH term(s)	Cell Compartmentation ; Cells, Cultured ; Endothelial Cells/chemistry ; Endothelial Cells/metabolism ; Endothelium, Vascular/cytology ; Humans ; Leukotriene B4/pharmacology ; Lipopolysaccharides/pharmacology ; Receptors, Leukotriene/analysis ; Receptors, Leukotriene B4/analysis ; Receptors, Leukotriene B4/genetics ; Up-Regulation/drug effects
Chemical Substances	LTB4R protein, human ; LTB4R2 protein, human ; Lipopolysaccharides ; Receptors, Leukotriene ; Receptors, Leukotriene B4 ; Leukotriene B4 (1HGW4DR56D)
Language	English
Publishing date	2010-10-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1493-x
ISSN	1090-2422 ; 0014-4827
ISSN (online)	1090-2422
ISSN	0014-4827
DOI	10.1016/j.yexcr.2010.07.016
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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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