The Experts below are selected from a list of 225 Experts worldwide ranked by ideXlab platform
Sirpa Jalkanen - One of the best experts on this subject based on the ideXlab platform.
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Cloning of Vascular Adhesion Protein 1 Reveals a Novel Multifunctional Adhesion Molecule
2013Co-Authors: J. Smith, Marko Salmi, Petri Bono, Jukka Hellman, Taina Leu, Sirpa JalkanenAbstract:Vascular adhesion protein 1 (VAP-1) is a human endothelial sialoglycoprotein whose cell surface expression is induced under inflammatory conditions. It has been shown previously to participate in Lymphocyte Recirculation by mediating the binding of Lymphocytes to peripheral lymph node vascular endothelial cells in an L-selectin–independent fashion. We report here that the VAP-1 cDNA encodes a type II transmembrane protein of 84.6 kD with a single transmembrane domain located at the NH2-terminal end of the molecule and six potential N-glycosylation sites in the extracellular domain. In vivo, the protein exists predominantly as a homodimer of 170–180 kD. Ax endothelial cells transfected with a VAP-1 cDNA express VAP-1 on their cell surface and bind Lymphocytes, and the binding can be partially inhibited with anti–VAP-1 mAbs. VAP-1 has no similarity to any currently known adhesion molecules, but has significant identity to the copper-containing amine oxidase family and has a monoamine oxidase activity. We propose that VAP-1 is a novel type of adhesion molecule with dual function. With the appropriate glycosylation and in the correct inflammatory setting, its expression on the lumenal endothelial cell surface allows it to mediate Lymphocyte adhesion and to function as an adhesion receptor involved in Lymphocyte Recirculation. Its primary function i
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Molecules controlling Lymphocyte migration to the gut
Gut, 1999Co-Authors: Marko Salmi, Sirpa JalkanenAbstract:Continuous Lymphocyte migration to normal gut is a prerequisite for immune homoeostasis in humans. In this review we briefly describe the physiology of Lymphocyte Recirculation through the bowel. The adhesion molecules mediating the Lymphocyte–endothelial interactions in the gut during the multistep extravasation cascade will be presented in the light of their ability to confer mucosal selectivity of Lymphocyte trafficking. We will also discuss the relevance of leucocyte Recirculation in respect to bowel inflammation and mucosal vaccination, and its potential in the anti-inflammatory treatment of gastrointestinal diseases. The gut is the main portal of antigen entry into the body and Lymphocytes are responsible for mounting an adequate immune response against harmful antigens. As each Lymphocyte only carries an antigen receptor for a single antigen, a huge number of Lymphocytes, each specific for a different antigen, are produced in the bone marrow and thymus each day. These naive cells must then be able to sample freely all different tissues of the body in search of their cognate antigens. To maximise the likelyhood of the rare possibility that a given Lymphocyte would find its cognate antigen introduced anywhere in the body, a sophisticated system of Lymphocyte Recirculation has evolved.1-4 In this process, Lymphocytes continuously patrol between the blood and different tissues of the body. Initially blood borne Lymphocytes leave the circulation via secondary lymphoid tissues like lymph nodes. The exit from the blood mainly takes place in distinct postcapillary vessels called high endothelial venules (HEV), which display several unique structural and functional modifications to facilitate extravasation.5 Foreign antigens are retrieved and concentrated from distal epithelial surfaces via the afferent lymphatic system into the secondary lymphoid organs. When an extravasated Lymphocyte finds its antigen in the supportive context of the secondary lymphoid tissues, it starts to proliferate and differentiate and gives rise …
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Cloning of Vascular Adhesion Protein 1 Reveals a Novel Multifunctional Adhesion Molecule
The Journal of experimental medicine, 1998Co-Authors: David J. Smith, Marko Salmi, Petri Bono, Jukka Hellman, Taina Leu, Sirpa JalkanenAbstract:Vascular adhesion protein 1 (VAP-1) is a human endothelial sialoglycoprotein whose cell surface expression is induced under inflammatory conditions. It has been shown previously to participate in Lymphocyte Recirculation by mediating the binding of Lymphocytes to peripheral lymph node vascular endothelial cells in an L-selectin–independent fashion. We report here that the VAP-1 cDNA encodes a type II transmembrane protein of 84.6 kD with a single transmembrane domain located at the NH2-terminal end of the molecule and six potential N-glycosylation sites in the extracellular domain. In vivo, the protein exists predominantly as a homodimer of 170–180 kD. Ax endothelial cells transfected with a VAP-1 cDNA express VAP-1 on their cell surface and bind Lymphocytes, and the binding can be partially inhibited with anti–VAP-1 mAbs. VAP-1 has no similarity to any currently known adhesion molecules, but has significant identity to the copper-containing amine oxidase family and has a monoamine oxidase activity. We propose that VAP-1 is a novel type of adhesion molecule with dual function. With the appropriate glycosylation and in the correct inflammatory setting, its expression on the lumenal endothelial cell surface allows it to mediate Lymphocyte adhesion and to function as an adhesion receptor involved in Lymphocyte Recirculation. Its primary function in other locations where it is expressed, such as smooth muscle, may depend on its inherent monoamine oxidase activity.
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How do Lymphocytes know where to go: current concepts and enigmas of Lymphocyte homing.
Advances in immunology, 1997Co-Authors: Marko Salmi, Sirpa JalkanenAbstract:Publisher Summary This chapter explores the field of investigation that has combined in an effective way the power of new technologies including recombinant DNA technology and methods of glycobiology to analyze the multidimensional phenomenon of Lymphocyte Recirculation. A useful working model of Lymphocyte extravasation cascade has been compiled based on numerous elegant in vitro and in vivo studies. This paradigm envisions Lymphocyte emigration as a multistep process with sequential but partially overlapping stages of interaction between the Lymphocyte and the vascular lining. The chapter illustrates that the Lymphocyte homing studies began from the observation of tissue selective Recirculation of immunoblasts. Almost all Lymphocyte homing experiments have been done with T cells. The chapter illustrates that there are a few studies on the mechanisms of Lymphocyte transmigration through the vessel wall, its chemotactic and haptotactic movements within the tissue stroma, its intraorgan segregation into discrete lymphoid areas, and its exit into the efferent lymphatic system. Reconstitution of these stages of Lymphocyte Recirculation can be a real methodological and intellectual challenge in the coming years.
Marko Salmi - One of the best experts on this subject based on the ideXlab platform.
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Cloning of Vascular Adhesion Protein 1 Reveals a Novel Multifunctional Adhesion Molecule
2013Co-Authors: J. Smith, Marko Salmi, Petri Bono, Jukka Hellman, Taina Leu, Sirpa JalkanenAbstract:Vascular adhesion protein 1 (VAP-1) is a human endothelial sialoglycoprotein whose cell surface expression is induced under inflammatory conditions. It has been shown previously to participate in Lymphocyte Recirculation by mediating the binding of Lymphocytes to peripheral lymph node vascular endothelial cells in an L-selectin–independent fashion. We report here that the VAP-1 cDNA encodes a type II transmembrane protein of 84.6 kD with a single transmembrane domain located at the NH2-terminal end of the molecule and six potential N-glycosylation sites in the extracellular domain. In vivo, the protein exists predominantly as a homodimer of 170–180 kD. Ax endothelial cells transfected with a VAP-1 cDNA express VAP-1 on their cell surface and bind Lymphocytes, and the binding can be partially inhibited with anti–VAP-1 mAbs. VAP-1 has no similarity to any currently known adhesion molecules, but has significant identity to the copper-containing amine oxidase family and has a monoamine oxidase activity. We propose that VAP-1 is a novel type of adhesion molecule with dual function. With the appropriate glycosylation and in the correct inflammatory setting, its expression on the lumenal endothelial cell surface allows it to mediate Lymphocyte adhesion and to function as an adhesion receptor involved in Lymphocyte Recirculation. Its primary function i
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Molecules controlling Lymphocyte migration to the gut
Gut, 1999Co-Authors: Marko Salmi, Sirpa JalkanenAbstract:Continuous Lymphocyte migration to normal gut is a prerequisite for immune homoeostasis in humans. In this review we briefly describe the physiology of Lymphocyte Recirculation through the bowel. The adhesion molecules mediating the Lymphocyte–endothelial interactions in the gut during the multistep extravasation cascade will be presented in the light of their ability to confer mucosal selectivity of Lymphocyte trafficking. We will also discuss the relevance of leucocyte Recirculation in respect to bowel inflammation and mucosal vaccination, and its potential in the anti-inflammatory treatment of gastrointestinal diseases. The gut is the main portal of antigen entry into the body and Lymphocytes are responsible for mounting an adequate immune response against harmful antigens. As each Lymphocyte only carries an antigen receptor for a single antigen, a huge number of Lymphocytes, each specific for a different antigen, are produced in the bone marrow and thymus each day. These naive cells must then be able to sample freely all different tissues of the body in search of their cognate antigens. To maximise the likelyhood of the rare possibility that a given Lymphocyte would find its cognate antigen introduced anywhere in the body, a sophisticated system of Lymphocyte Recirculation has evolved.1-4 In this process, Lymphocytes continuously patrol between the blood and different tissues of the body. Initially blood borne Lymphocytes leave the circulation via secondary lymphoid tissues like lymph nodes. The exit from the blood mainly takes place in distinct postcapillary vessels called high endothelial venules (HEV), which display several unique structural and functional modifications to facilitate extravasation.5 Foreign antigens are retrieved and concentrated from distal epithelial surfaces via the afferent lymphatic system into the secondary lymphoid organs. When an extravasated Lymphocyte finds its antigen in the supportive context of the secondary lymphoid tissues, it starts to proliferate and differentiate and gives rise …
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Cloning of Vascular Adhesion Protein 1 Reveals a Novel Multifunctional Adhesion Molecule
The Journal of experimental medicine, 1998Co-Authors: David J. Smith, Marko Salmi, Petri Bono, Jukka Hellman, Taina Leu, Sirpa JalkanenAbstract:Vascular adhesion protein 1 (VAP-1) is a human endothelial sialoglycoprotein whose cell surface expression is induced under inflammatory conditions. It has been shown previously to participate in Lymphocyte Recirculation by mediating the binding of Lymphocytes to peripheral lymph node vascular endothelial cells in an L-selectin–independent fashion. We report here that the VAP-1 cDNA encodes a type II transmembrane protein of 84.6 kD with a single transmembrane domain located at the NH2-terminal end of the molecule and six potential N-glycosylation sites in the extracellular domain. In vivo, the protein exists predominantly as a homodimer of 170–180 kD. Ax endothelial cells transfected with a VAP-1 cDNA express VAP-1 on their cell surface and bind Lymphocytes, and the binding can be partially inhibited with anti–VAP-1 mAbs. VAP-1 has no similarity to any currently known adhesion molecules, but has significant identity to the copper-containing amine oxidase family and has a monoamine oxidase activity. We propose that VAP-1 is a novel type of adhesion molecule with dual function. With the appropriate glycosylation and in the correct inflammatory setting, its expression on the lumenal endothelial cell surface allows it to mediate Lymphocyte adhesion and to function as an adhesion receptor involved in Lymphocyte Recirculation. Its primary function in other locations where it is expressed, such as smooth muscle, may depend on its inherent monoamine oxidase activity.
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How do Lymphocytes know where to go: current concepts and enigmas of Lymphocyte homing.
Advances in immunology, 1997Co-Authors: Marko Salmi, Sirpa JalkanenAbstract:Publisher Summary This chapter explores the field of investigation that has combined in an effective way the power of new technologies including recombinant DNA technology and methods of glycobiology to analyze the multidimensional phenomenon of Lymphocyte Recirculation. A useful working model of Lymphocyte extravasation cascade has been compiled based on numerous elegant in vitro and in vivo studies. This paradigm envisions Lymphocyte emigration as a multistep process with sequential but partially overlapping stages of interaction between the Lymphocyte and the vascular lining. The chapter illustrates that the Lymphocyte homing studies began from the observation of tissue selective Recirculation of immunoblasts. Almost all Lymphocyte homing experiments have been done with T cells. The chapter illustrates that there are a few studies on the mechanisms of Lymphocyte transmigration through the vessel wall, its chemotactic and haptotactic movements within the tissue stroma, its intraorgan segregation into discrete lymphoid areas, and its exit into the efferent lymphatic system. Reconstitution of these stages of Lymphocyte Recirculation can be a real methodological and intellectual challenge in the coming years.
Vitaly V. Ganusov - One of the best experts on this subject based on the ideXlab platform.
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Estimating Residence Times of Lymphocytes in Ovine Lymph Nodes.
Frontiers in immunology, 2019Co-Authors: Margaret M. Mcdaniel, Vitaly V. GanusovAbstract:The ability of Lymphocytes to recirculate between blood and secondary lymphoid tissues such as lymph nodes (LNs) and spleen is well established. Sheep have been used as an experimental system to study Lymphocyte Recirculation for decades and multiple studies document accumulation and loss of intravenously (i.v.) transferred Lymphocytes in efferent lymph of various ovine LNs. Yet, surprisingly little work has been done to accurately quantify the dynamics of Lymphocyte exit from the LNs and to estimate the average residence times of Lymphocytes in ovine LNs. In this work we developed a series of mathematical models based on fundamental principles of Lymphocyte Recirculation in the body under non-inflammatory (resting) conditions. Our analysis suggested that in sheep, recirculating Lymphocytes spend on average 3 h in the spleen and 20 h in skin or gut-draining LNs with a distribution of residence times in LNs following a skewed gamma (lognormal-like) distribution. Our mathematical models also suggested an explanation for a puzzling observation of the long-term persistence of i.v. transferred Lymphocytes in the efferent lymph of the prescapular LN (pLN); the model predicted that this is a natural consequence of long-term persistence of the transferred Lymphocytes in circulation. We also found that Lymphocytes isolated from the skin-draining pLN have a 2-fold increased entry rate into the pLN as opposed to the mesenteric (gut-draining) LN (mLN). Likewise, Lymphocytes from mLN had a 3-fold increased entry rate into the mLN as opposed to entry rate into pLN. In contrast, these cannulation data could not be explained by preferential retention of cells in LNs of their origin. Taken together, our work illustrates the power of mathematical modeling in describing the kinetics of Lymphocyte migration in sheep and provides quantitative estimates of Lymphocyte residence times in ovine LNs.
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Experimental and mathematical approaches to quantify Recirculation kinetics of Lymphocytes
2018Co-Authors: Vitaly V. Ganusov, Michio TomuraAbstract:One of the properties of the immune system that makes it different from nervous and endocrine systems of mammals is the ability of immune cells to migrate between different tissues. Lymphocytes such as T and B cells have the ability to migrate from the blood to secondary lymphoid tissues such as spleen, lymph nodes, and Peyer's patches, and then migrate back to the blood, i.e., they can recirculate. Recirculation of Lymphocytes has been a subject of intensive investigation decades ago with wealth of data on the kinetics of Lymphocyte Recirculation available. However, these data have not been widely used to estimate the kinetics of Recirculation of different Lymphocyte subsets in naive and immunized animals. In this paper we review pioneering studies addressing the question of Lymphocyte Recirculation, discuss quantitative approaches that have been used to estimate the kinetics of Lymphocyte Recirculation, and suggest steps for further refining of estimates of residence times of T and B Lymphocytes in tissues.
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Mathematical modeling reveals kinetics of Lymphocyte Recirculation in the whole organism.
PLoS computational biology, 2014Co-Authors: Vitaly V. Ganusov, Jeremy AuerbachAbstract:The kinetics of Recirculation of naive Lymphocytes in the body has important implications for the speed at which local infections are detected and controlled by immune responses. With a help of a novel mathematical model, we analyze experimental data on migration of 51Cr-labeled thoracic duct Lymphocytes (TDLs) via major lymphoid and nonlymphoid tissues of rats in the absence of systemic antigenic stimulation. We show that at any point of time, 95% of Lymphocytes in the blood travel via capillaries in the lung or sinusoids of the liver and only 5% migrate to secondary lymphoid tissues such as lymph nodes, Peyer's patches, or the spleen. Interestingly, our analysis suggests that Lymphocytes travel via lung capillaries and liver sinusoids at an extremely rapid rate with the average residence time in these tissues being less than 1 minute. The model also predicts a relatively short average residence time of TDLs in the spleen (2.5 hours) and a longer average residence time of TDLs in major lymph nodes and Peyer's patches (10 hours). Surprisingly, we find that the average residence time of Lymphocytes is similar in lymph nodes draining the skin (subcutaneous LNs) or the gut (mesenteric LNs) or in Peyer's patches. Applying our model to an additional dataset on Lymphocyte migration via resting and antigen-stimulated lymph nodes we find that enlargement of antigen-stimulated lymph nodes occurs mainly due to increased entrance rate of TDLs into the nodes and not due to decreased exit rate as has been suggested in some studies. Taken together, our analysis for the first time provides a comprehensive, systems view of Recirculation kinetics of thoracic duct Lymphocytes in the whole organism.
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Mathematical Modeling Reveals Kinetics of Lymphocyte Recirculation in the Whole Organism
2014Co-Authors: Lymphocyte Recirculation In The Whole, Vitaly V. Ganusov, Jeremy AuerbachAbstract:The kinetics of Recirculation of naive Lymphocytes in the body has important implications for the speed at which local infections are detected and controlled by immune responses. With a help of a novel mathematical model, we analyze experimental data on migration of 51Cr-labeled thoracic duct Lymphocytes (TDLs) via major lymphoid and nonlymphoid tissues of rats in the absence of systemic antigenic stimulation. We show that at any point of time, 95 % of Lymphocytes in the blood travel via capillaries in the lung or sinusoids of the liver and only 5 % migrate to secondary lymphoid tissues such as lymph nodes, Peyer’s patches, or the spleen. Interestingly, our analysis suggests that Lymphocytes travel via lung capillaries and liver sinusoids at an extremely rapid rate with the average residence time in these tissues being less than 1 minute. The model also predicts a relatively short average residence time of TDLs in the spleen (2.5 hours) and a longer average residence time of TDLs in major lymph nodes and Peyer’s patches (10 hours). Surprisingly, we find that the average residence time of Lymphocytes is similar in lymph nodes draining the skin (subcutaneous LNs) or the gut (mesenteric LNs) or in Peyer’s patches. Applying our model to an additional dataset on Lymphocyte migration via resting and antigen-stimulated lymph nodes we find that enlargement of antigen-stimulated lymph nodes occurs mainly due to increased entrance rate of TDLs into the nodes and not due to decreased exit rate as has been suggested in some studies. Taken together, our analysis for the first time provides a comprehensive, systems view of Recirculation kinetics of thoracic duc
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Mathematical model accurately predicts the hierarchy of Recirculation of thoracic duct Lymphocytes (TDLs) between major murine organs.
2014Co-Authors: Vitaly V. Ganusov, Jeremy AuerbachAbstract:Cr-labeled TDLs were passaged via an intermediate host and then were transferred into syngenic rats (Figure 1A). The percent of transferred cells was measured at different times after cell transfer in major lymphoid and nonlymphoid murine organs and is shown by markers. We fit the mathematical model of Lymphocyte Recirculation (eqn. (1) – (6)) to these experimental data using nonlinear least squares; model fits are shown as lines. Plots are for the first 30 minutes of the experiment (A) or for the whole experiment (B, abscissa values are plotted on the log-scale). Parameter estimates of the model are given in Table 1. Different y-scales in panels A and B were used for clarity.
Jeremy Auerbach - One of the best experts on this subject based on the ideXlab platform.
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Mathematical modeling reveals kinetics of Lymphocyte Recirculation in the whole organism.
PLoS computational biology, 2014Co-Authors: Vitaly V. Ganusov, Jeremy AuerbachAbstract:The kinetics of Recirculation of naive Lymphocytes in the body has important implications for the speed at which local infections are detected and controlled by immune responses. With a help of a novel mathematical model, we analyze experimental data on migration of 51Cr-labeled thoracic duct Lymphocytes (TDLs) via major lymphoid and nonlymphoid tissues of rats in the absence of systemic antigenic stimulation. We show that at any point of time, 95% of Lymphocytes in the blood travel via capillaries in the lung or sinusoids of the liver and only 5% migrate to secondary lymphoid tissues such as lymph nodes, Peyer's patches, or the spleen. Interestingly, our analysis suggests that Lymphocytes travel via lung capillaries and liver sinusoids at an extremely rapid rate with the average residence time in these tissues being less than 1 minute. The model also predicts a relatively short average residence time of TDLs in the spleen (2.5 hours) and a longer average residence time of TDLs in major lymph nodes and Peyer's patches (10 hours). Surprisingly, we find that the average residence time of Lymphocytes is similar in lymph nodes draining the skin (subcutaneous LNs) or the gut (mesenteric LNs) or in Peyer's patches. Applying our model to an additional dataset on Lymphocyte migration via resting and antigen-stimulated lymph nodes we find that enlargement of antigen-stimulated lymph nodes occurs mainly due to increased entrance rate of TDLs into the nodes and not due to decreased exit rate as has been suggested in some studies. Taken together, our analysis for the first time provides a comprehensive, systems view of Recirculation kinetics of thoracic duct Lymphocytes in the whole organism.
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Mathematical Modeling Reveals Kinetics of Lymphocyte Recirculation in the Whole Organism
2014Co-Authors: Lymphocyte Recirculation In The Whole, Vitaly V. Ganusov, Jeremy AuerbachAbstract:The kinetics of Recirculation of naive Lymphocytes in the body has important implications for the speed at which local infections are detected and controlled by immune responses. With a help of a novel mathematical model, we analyze experimental data on migration of 51Cr-labeled thoracic duct Lymphocytes (TDLs) via major lymphoid and nonlymphoid tissues of rats in the absence of systemic antigenic stimulation. We show that at any point of time, 95 % of Lymphocytes in the blood travel via capillaries in the lung or sinusoids of the liver and only 5 % migrate to secondary lymphoid tissues such as lymph nodes, Peyer’s patches, or the spleen. Interestingly, our analysis suggests that Lymphocytes travel via lung capillaries and liver sinusoids at an extremely rapid rate with the average residence time in these tissues being less than 1 minute. The model also predicts a relatively short average residence time of TDLs in the spleen (2.5 hours) and a longer average residence time of TDLs in major lymph nodes and Peyer’s patches (10 hours). Surprisingly, we find that the average residence time of Lymphocytes is similar in lymph nodes draining the skin (subcutaneous LNs) or the gut (mesenteric LNs) or in Peyer’s patches. Applying our model to an additional dataset on Lymphocyte migration via resting and antigen-stimulated lymph nodes we find that enlargement of antigen-stimulated lymph nodes occurs mainly due to increased entrance rate of TDLs into the nodes and not due to decreased exit rate as has been suggested in some studies. Taken together, our analysis for the first time provides a comprehensive, systems view of Recirculation kinetics of thoracic duc
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Mathematical model accurately predicts the hierarchy of Recirculation of thoracic duct Lymphocytes (TDLs) between major murine organs.
2014Co-Authors: Vitaly V. Ganusov, Jeremy AuerbachAbstract:Cr-labeled TDLs were passaged via an intermediate host and then were transferred into syngenic rats (Figure 1A). The percent of transferred cells was measured at different times after cell transfer in major lymphoid and nonlymphoid murine organs and is shown by markers. We fit the mathematical model of Lymphocyte Recirculation (eqn. (1) – (6)) to these experimental data using nonlinear least squares; model fits are shown as lines. Plots are for the first 30 minutes of the experiment (A) or for the whole experiment (B, abscissa values are plotted on the log-scale). Parameter estimates of the model are given in Table 1. Different y-scales in panels A and B were used for clarity.
Martin Lipp - One of the best experts on this subject based on the ideXlab platform.
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Concerted action of the chemokine and lymphotoxin system in secondary lymphoid-organ development.
Current opinion in immunology, 2003Co-Authors: Gerd Müller, Martin LippAbstract:Chemokines are essential regulators of Lymphocyte migration throughout the body. The chemokine system controls Lymphocyte Recirculation in immune-system homeostasis, as well as the activation-dependent and tissue-selective trafficking of effector and memory Lymphocytes during immune responses. In addition, there is now substantial evidence that chemokines are critical factors for the development and organization of secondary lymphoid organs and that they are involved in all stages of lymphoid organogenesis.
