The Experts below are selected from a list of 39585 Experts worldwide ranked by ideXlab platform
Yoshiro Maru - One of the best experts on this subject based on the ideXlab platform.
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the s100a8 serum amyloid a3 tlr4 paracrine cascade establishes a pre metastatic phase
Nature Cell Biology, 2008Co-Authors: Sachie Hiratsuka, Hiroyuki Aburatani, Akira Watanabe, Yoshiko Sakurai, Sachiko Akashitakamura, Sachie Ishibashi, Kensuke Miyake, Masabumi Shibuya, Shizuo Akira, Yoshiro MaruAbstract:The production of Chemoattractants in the pre-metastatic lung can be induced by distant primary tumours. The Chemoattractants S100A8 and S100A9 induce serum amyloid A3 and TLR4 activation and cause an inflammation-like state that facilitates metastasis. A large number of macrophages and haematopoietic progenitor cells accumulate in pre-metastatic lungs1,2 in which Chemoattractants, such as S100A8 and S100A9, are produced by distant primary tumours serving as metastatic soil3. The exact mechanism by which these Chemoattractants elicit cell accumulation is not known. Here, we show that serum amyloid A (SAA) 3, which is induced in pre-metastatic lungs by S100A8 and S100A9, has a role in the accumulation of myeloid cells and acts as a positive-feedback regulator for Chemoattractant secretion. We also show that in lung endothelial cells and macrophages, Toll-like receptor (TLR) 4 acts as a functional receptor for SAA3 in the pre-metastatic phase. In our study, SAA3 stimulated NF-κB signalling in a TLR4-dependent manner and facilitated metastasis. This inflammation-like state accelerated the migration of primary tumour cells to lung tissues, but this was suppressed by the inhibition of either TLR4 or SAA3. Thus, blocking SAA3–TLR4 function in the pre-metastatic phase could prove to be an effective strategy for the prevention of pulmonary metastasis.
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the s100a8 serum amyloid a3 tlr4 paracrine cascade establishes a pre metastatic phase
Nature Cell Biology, 2008Co-Authors: Sachie Hiratsuka, Hiroyuki Aburatani, Akira Watanabe, Yoshiko Sakurai, Sachiko Akashitakamura, Sachie Ishibashi, Kensuke Miyake, Masabumi Shibuya, Shizuo Akira, Yoshiro MaruAbstract:A large number of macrophages and haematopoietic progenitor cells accumulate in pre-metastatic lungs in which Chemoattractants, such as S100A8 and S100A9, are produced by distant primary tumours serving as metastatic soil. The exact mechanism by which these Chemoattractants elicit cell accumulation is not known. Here, we show that serum amyloid A (SAA) 3, which is induced in pre-metastatic lungs by S100A8 and S100A9, has a role in the accumulation of myeloid cells and acts as a positive-feedback regulator for Chemoattractant secretion. We also show that in lung endothelial cells and macrophages, Toll-like receptor (TLR) 4 acts as a functional receptor for SAA3 in the pre-metastatic phase. In our study, SAA3 stimulated NF-kappaB signalling in a TLR4-dependent manner and facilitated metastasis. This inflammation-like state accelerated the migration of primary tumour cells to lung tissues, but this was suppressed by the inhibition of either TLR4 or SAA3. Thus, blocking SAA3-TLR4 function in the pre-metastatic phase could prove to be an effective strategy for the prevention of pulmonary metastasis.
Janina Ratajczak - One of the best experts on this subject based on the ideXlab platform.
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novel insight into stem cell mobilization plasma sphingosine 1 phosphate is a major Chemoattractant that directs the egress of hematopoietic stem progenitor cells from the bone marrow and its level in peripheral blood increases during mobilization du
Leukemia, 2010Co-Authors: Mariusz Z. Ratajczak, Marcin Wysoczynski, Magda Kucia, Anna Janowskawieczorek, Wojciech Marlicz, Mary J Laughlin, Janina RatajczakAbstract:Complement cascade (CC) becomes activated and its cleavage fragments play a crucial role in the mobilization of hematopoietic stem/progenitor cells (HSPCs). Here, we sought to determine which major chemottractant present in peripheral blood (PB) is responsible for the egress of HSPCs from the BM. We noticed that normal and mobilized plasma strongly chemoattracts HSPCs in a stromal derived factor-1 (SDF-1)-independent manner because i) plasma SDF-1 level does not correlate with mobilization efficiency, ii) the chemotactic plasma gradient is not affected in the presence of AMD3100, and iii) it is resistant to denaturation by heat. Surprisingly, the observed loss of plasma chemotactic activity after charcoal stripping suggested involvement of bioactive lipids and we focused on sphingosine-1 phosphate (S1P), a known chemoattracant of HSPCs. We found that S1P i) creates in plasma a continuously present gradient for BM-residing HSPCs, ii) is at physiologically relevant concentrations a Chemoattractant several magnitudes stronger than SDF-1, and iii) its plasma level increases during mobilization due to CC activation and the interaction of membrane attack complex (MAC) with erythrocytes that are a major reservoir of S1P. We conclude and propose a new paradigm that S1P is a crucial Chemoattractant for BM-residing HSPCs and that CC via MAC induces release of S1P from erythrocytes for optimal egress/mobilization of HSPCs.
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novel insight into stem cell mobilization plasma sphingosine 1 phosphate is a major Chemoattractant that directs the egress of hematopoietic stem progenitor cells from the bone marrow and its level in peripheral blood increases during mobilization du
Leukemia, 2010Co-Authors: Mariusz Z. Ratajczak, Marcin Wysoczynski, Wu Wan, Magda Kucia, Hakmo Lee, Anna Janowskawieczorek, Wojciech Marlicz, Mary J Laughlin, Janina RatajczakAbstract:The complement cascade (CC) becomes activated and its cleavage fragments play a crucial role in the mobilization of hematopoietic stem/progenitor cells (HSPCs). Here, we sought to determine which major Chemoattractant present in peripheral blood (PB) is responsible for the egress of HSPCs from the bone marrow (BM). We noticed that normal and mobilized plasma strongly chemoattracts HSPCs in a stromal-derived factor-1 (SDF-1)-independent manner because (i) plasma SDF-1 level does not correlate with mobilization efficiency; (ii) the chemotactic plasma gradient is not affected in the presence of AMD3100 and (iii) it is resistant to denaturation by heat. Surprisingly, the observed loss of plasma chemotactic activity after charcoal stripping suggested the involvement of bioactive lipids and we focused on sphingosine-1-phosphate (S1P), a known chemoattracant of HSPCs. We found that S1P (i) creates in plasma a continuously present gradient for BM-residing HSPCs; (ii) is at physiologically relevant concentrations a Chemoattractant several magnitudes stronger than SDF-1 and (iii) its plasma level increases during mobilization due to CC activation and interaction of the membrane attack complex (MAC) with erythrocytes that are a major reservoir of S1P. We conclude and propose a new paradigm that S1P is a crucial Chemoattractant for BM-residing HSPCs and that CC through MAC induces the release of S1P from erythrocytes for optimal egress/mobilization of HSPCs.
Sachie Hiratsuka - One of the best experts on this subject based on the ideXlab platform.
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the s100a8 serum amyloid a3 tlr4 paracrine cascade establishes a pre metastatic phase
Nature Cell Biology, 2008Co-Authors: Sachie Hiratsuka, Hiroyuki Aburatani, Akira Watanabe, Yoshiko Sakurai, Sachiko Akashitakamura, Sachie Ishibashi, Kensuke Miyake, Masabumi Shibuya, Shizuo Akira, Yoshiro MaruAbstract:The production of Chemoattractants in the pre-metastatic lung can be induced by distant primary tumours. The Chemoattractants S100A8 and S100A9 induce serum amyloid A3 and TLR4 activation and cause an inflammation-like state that facilitates metastasis. A large number of macrophages and haematopoietic progenitor cells accumulate in pre-metastatic lungs1,2 in which Chemoattractants, such as S100A8 and S100A9, are produced by distant primary tumours serving as metastatic soil3. The exact mechanism by which these Chemoattractants elicit cell accumulation is not known. Here, we show that serum amyloid A (SAA) 3, which is induced in pre-metastatic lungs by S100A8 and S100A9, has a role in the accumulation of myeloid cells and acts as a positive-feedback regulator for Chemoattractant secretion. We also show that in lung endothelial cells and macrophages, Toll-like receptor (TLR) 4 acts as a functional receptor for SAA3 in the pre-metastatic phase. In our study, SAA3 stimulated NF-κB signalling in a TLR4-dependent manner and facilitated metastasis. This inflammation-like state accelerated the migration of primary tumour cells to lung tissues, but this was suppressed by the inhibition of either TLR4 or SAA3. Thus, blocking SAA3–TLR4 function in the pre-metastatic phase could prove to be an effective strategy for the prevention of pulmonary metastasis.
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the s100a8 serum amyloid a3 tlr4 paracrine cascade establishes a pre metastatic phase
Nature Cell Biology, 2008Co-Authors: Sachie Hiratsuka, Hiroyuki Aburatani, Akira Watanabe, Yoshiko Sakurai, Sachiko Akashitakamura, Sachie Ishibashi, Kensuke Miyake, Masabumi Shibuya, Shizuo Akira, Yoshiro MaruAbstract:A large number of macrophages and haematopoietic progenitor cells accumulate in pre-metastatic lungs in which Chemoattractants, such as S100A8 and S100A9, are produced by distant primary tumours serving as metastatic soil. The exact mechanism by which these Chemoattractants elicit cell accumulation is not known. Here, we show that serum amyloid A (SAA) 3, which is induced in pre-metastatic lungs by S100A8 and S100A9, has a role in the accumulation of myeloid cells and acts as a positive-feedback regulator for Chemoattractant secretion. We also show that in lung endothelial cells and macrophages, Toll-like receptor (TLR) 4 acts as a functional receptor for SAA3 in the pre-metastatic phase. In our study, SAA3 stimulated NF-kappaB signalling in a TLR4-dependent manner and facilitated metastasis. This inflammation-like state accelerated the migration of primary tumour cells to lung tissues, but this was suppressed by the inhibition of either TLR4 or SAA3. Thus, blocking SAA3-TLR4 function in the pre-metastatic phase could prove to be an effective strategy for the prevention of pulmonary metastasis.
Mariusz Z. Ratajczak - One of the best experts on this subject based on the ideXlab platform.
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novel insight into stem cell mobilization plasma sphingosine 1 phosphate is a major Chemoattractant that directs the egress of hematopoietic stem progenitor cells from the bone marrow and its level in peripheral blood increases during mobilization du
Leukemia, 2010Co-Authors: Mariusz Z. Ratajczak, Marcin Wysoczynski, Magda Kucia, Anna Janowskawieczorek, Wojciech Marlicz, Mary J Laughlin, Janina RatajczakAbstract:Complement cascade (CC) becomes activated and its cleavage fragments play a crucial role in the mobilization of hematopoietic stem/progenitor cells (HSPCs). Here, we sought to determine which major chemottractant present in peripheral blood (PB) is responsible for the egress of HSPCs from the BM. We noticed that normal and mobilized plasma strongly chemoattracts HSPCs in a stromal derived factor-1 (SDF-1)-independent manner because i) plasma SDF-1 level does not correlate with mobilization efficiency, ii) the chemotactic plasma gradient is not affected in the presence of AMD3100, and iii) it is resistant to denaturation by heat. Surprisingly, the observed loss of plasma chemotactic activity after charcoal stripping suggested involvement of bioactive lipids and we focused on sphingosine-1 phosphate (S1P), a known chemoattracant of HSPCs. We found that S1P i) creates in plasma a continuously present gradient for BM-residing HSPCs, ii) is at physiologically relevant concentrations a Chemoattractant several magnitudes stronger than SDF-1, and iii) its plasma level increases during mobilization due to CC activation and the interaction of membrane attack complex (MAC) with erythrocytes that are a major reservoir of S1P. We conclude and propose a new paradigm that S1P is a crucial Chemoattractant for BM-residing HSPCs and that CC via MAC induces release of S1P from erythrocytes for optimal egress/mobilization of HSPCs.
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novel insight into stem cell mobilization plasma sphingosine 1 phosphate is a major Chemoattractant that directs the egress of hematopoietic stem progenitor cells from the bone marrow and its level in peripheral blood increases during mobilization du
Leukemia, 2010Co-Authors: Mariusz Z. Ratajczak, Marcin Wysoczynski, Wu Wan, Magda Kucia, Hakmo Lee, Anna Janowskawieczorek, Wojciech Marlicz, Mary J Laughlin, Janina RatajczakAbstract:The complement cascade (CC) becomes activated and its cleavage fragments play a crucial role in the mobilization of hematopoietic stem/progenitor cells (HSPCs). Here, we sought to determine which major Chemoattractant present in peripheral blood (PB) is responsible for the egress of HSPCs from the bone marrow (BM). We noticed that normal and mobilized plasma strongly chemoattracts HSPCs in a stromal-derived factor-1 (SDF-1)-independent manner because (i) plasma SDF-1 level does not correlate with mobilization efficiency; (ii) the chemotactic plasma gradient is not affected in the presence of AMD3100 and (iii) it is resistant to denaturation by heat. Surprisingly, the observed loss of plasma chemotactic activity after charcoal stripping suggested the involvement of bioactive lipids and we focused on sphingosine-1-phosphate (S1P), a known chemoattracant of HSPCs. We found that S1P (i) creates in plasma a continuously present gradient for BM-residing HSPCs; (ii) is at physiologically relevant concentrations a Chemoattractant several magnitudes stronger than SDF-1 and (iii) its plasma level increases during mobilization due to CC activation and interaction of the membrane attack complex (MAC) with erythrocytes that are a major reservoir of S1P. We conclude and propose a new paradigm that S1P is a crucial Chemoattractant for BM-residing HSPCs and that CC through MAC induces the release of S1P from erythrocytes for optimal egress/mobilization of HSPCs.
Eugene C Butcher - One of the best experts on this subject based on the ideXlab platform.
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Chemoattractants extracellular proteases and the integrated host defense response
Experimental Hematology, 2006Co-Authors: Brian A Zabel, Joanna Cichy, Samantha J Allen, Tracy M Handel, Luis A Zuniga, Takao Ohyama, Eugene C ButcherAbstract:The host response to tissue injury and/or infection is dependent on the action of numerous extracellular proteases. Proteolytic cascades trigger blood clotting, fibrinolysis, and complement activation, while proteases released upon leukocyte degranulation are integral to the processes of inflammation and immunity. Modulation of effector protein activity by proteases provides a critical layer of posttranslational control that enables rapid enzymatic regulation of target proteins. This report reviews the emerging literature describing a novel class of proteolytic targets, leukocyte Chemoattractants, and, in particular, chemerin, a dendritic cell and macrophage Chemoattractant activated by serine proteases of the coagulation, fibrinolytic, and inflammatory cascades. As Chemoattractants are critical for both systemic leukocyte positioning by triggering integrin activation and subsequent recruitment from circulation, and local intratissue leukocyte positioning via chemotaxis, modulation of attractant activities by proteases may have profound effects on the immune response.
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chemerin activation by serine proteases of the coagulation fibrinolytic and inflammatory cascades
Journal of Biological Chemistry, 2005Co-Authors: Brian A Zabel, Joanna Cichy, Samantha J Allen, Paulina Kulig, Jessica A Allen, Tracy M Handel, Eugene C ButcherAbstract:Abstract Proteases function at every level in host defense, from regulating vascular hemostasis and inflammation to mobilizing the “rapid responder” leukocytes of the immune system by regulating the activities of various Chemoattractants. Recent studies implicate proteolysis in the activation of a ubiquitous plasma Chemoattractant, chemerin, a ligand for the G-protein-coupled receptor CMKLR1 present on plasmacytoid dendritic cells and macrophages. To define the pathophysiologic triggers of chemerin activity, we evaluated the ability of serum- and inflammation-associated proteases to cleave chemerin and stimulate CMKLR1-mediated chemotaxis. We showed that serine proteases factor XIIa and plasmin of the coagulation and fibrinolytic cascades, elastase and cathepsin G released from activated neutrophil granules and mast cell tryptase are all potent activators of chemerin. Activation results from cleavage of the labile carboxyl terminus of the Chemoattractant at any of several different sites. Activation of chemerin by the serine protease cascades that trigger rapid defenses in the body may direct CMKLR1-positive plasmacytoid dendritic cell and tissue macrophage recruitment to sterile sites of tissue damage, as well as trafficking to sites of infectious and allergic inflammation.
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integrating conflicting chemotactic signals the role of memory in leukocyte navigation
Journal of Cell Biology, 1999Co-Authors: Ellen F Foxman, Eugene C Butcher, Eric J KunkelAbstract:Leukocytes navigate through complex Chemoattractant arrays, and in so doing, they must migrate from one Chemoattractant source to another. By evaluating directional persistence and chemotaxis during neutrophil migration under agarose, we show that cells migrating away from a local Chemoattractant, against a gradient, display true chemotaxis to distant agonists, often behaving as if the local gradient were without effect. We describe two interrelated properties of migrating cells that allow this to occur. First, migrating leukocytes can integrate competing Chemoattractant signals, responding as if to the vector sum of the orienting signals present. Second, migrating cells display memory of their recent environment: cells' perception of the relative strength of orienting signals is influenced by their history, so that cells prioritize newly arising or newly encountered attractants. We propose that this cellular memory, by promoting sequential chemotaxis to one attractant after another, is in fact responsible for the integration of competitive orienting signals over time, and allows combinations of Chemoattractants to guide leukocytes in a step-by-step fashion to their destinations within tissues.
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evidence of ζ protein kinase c involvement in polymorphonuclear neutrophil integrin dependent adhesion and chemotaxis
Journal of Biological Chemistry, 1998Co-Authors: Carlo Laudanna, Daria Mochlyrosen, Tamar Liron, Gabriela Constantin, Eugene C ButcherAbstract:Classical Chemoattractants and chemokines trigger integrin-dependent adhesion of blood leukocytes to vascular endothelium and also direct subsequent extravasation and migration into tissues. In studies of human polymorphonuclear neutrophil responses to formyl peptides and to interleukin 8, we show evidence of involvement of the atypical ζ protein kinase C in the signaling pathway leading to Chemoattractant-triggered actin assembly, integrin-dependent adhesion, and chemotaxis. Selective inhibitors of classical and novel protein kinase C isozymes do not prevent Chemoattractant-induced neutrophil adhesion and chemotaxis. In contrast, chelerythrine chloride and synthetic myristoylated peptides with sequences based on the endogenous ζ protein kinase C pseudosubstrate region block agonist-induced adhesion to fibrinogen, chemotaxis and F-actin accumulation. Biochemical analysis shows that Chemoattractants trigger rapid translocation of ζ protein kinase C to the plasma membrane accompanied by rapid but transient increase of the kinase activity. Moreover, pretreatment with C3 transferase, a specific inhibitor of Rho small GTPases, blocks ζ but not α protein kinase C plasma membrane translocation. Synthetic peptides from ζ protein kinase C also inhibit phorbol ester-induced integrin-dependent adhesion but not NADPH-oxidase activation, and C3 transferase pretreatment blocks phorbol ester-triggered translocation of ζ but not α protein kinase C. These data suggest the involvement of ζ protein kinase C in Chemoattractant-induced leukocyte integrin-dependent adhesion and chemotaxis. Moreover, they highlight a potential link between atypical protein kinase C isozymes and Rho signaling pathways leading to integrin-activation.
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elevation of intracellular camp inhibits rhoa activation and integrin dependent leukocyte adhesion induced by Chemoattractants
Journal of Biological Chemistry, 1997Co-Authors: Carlo Laudanna, James J Campbell, Eugene C ButcherAbstract:Abstract Chemoattractant receptors of the serpentine, heterotrimeric Gαi protein-linked family can activate leukocyte integrins and in this role regulate leukocyte traffic and cell-cell interactions in immune and inflammatory responses. Using a mouse lymphoid cell line transfected with human formyl peptide or interleukin-8 receptors and normal human neutrophils as models, we show that cAMP functions as a gating element on the Chemoattractant-induced rho-dependent signaling pathway leading to leukocyte integrin activation and adhesion. cAMP, acting through protein kinase A, inhibits Chemoattractant-triggered integrin-dependent leukocyte adhesion. cAMP also prevents guanine nucleotide exchange on RhoA, a small GTP-binding protein of the rho subfamily, which is activated in seconds by Chemoattractants. In contrast, Chemoattractant-triggered intracellular calcium elevation is unaffected by cAMP, and cAMP has no effect on rho-dependent adhesion and RhoA guanine nucleotide exchange triggered through the independent protein kinase C pathway. These data suggest that cAMP-induced inhibition of rho activation may be responsible for the anti-adhesive effect of cAMP and may contribute to the anti-inflammatory activity of cAMP elevating agonists and drugs. Moreover, the findings extend the concept of cyclic nucleotide gating as a broadly important mechanism in the regulation of intracellular signaling pathways and the cellular activities they control.