Inflammatory Chemokine Transport and Presentation in HEV

Interstitial fluid is constantly drained into lymph nodes (LNs) via afferent lymph vessels. This conduit enables monocyte-derived macrophages and dendritic cells to access LNs from peripheral tissues. We show that during inflammation in the skin, a second recruitment pathway is evoked that recruits large numbers of blood-borne monocytes to LNs via high endothelial venules (HEVs). Inhibition of monocyte chemoattractant protein (MCP)-1 blocked this inflammation-induced monocyte homing to LNs. MCP-1 mRNA in inflamed skin was over 100-fold upregulated and paralleled MCP-1 protein levels, whereas in draining LNs MCP-1 mRNA induction was much weaker and occurred only after a pronounced rise in MCP-1 protein. Thus, MCP-1 in draining LNs was primarily derived from inflamed skin. In MCP-1−/− mice, intracutaneously injected MCP-1 accumulated rapidly in the draining LNs where it enhanced monocyte recruitment. Intravital microscopy showed that skin-derived MCP-1 was transported via the lymph to the luminal surface of HEVs where it triggered integrin-dependent arrest of rolling monocytes. These findings demonstrate that inflamed peripheral tissues project their local chemokine profile to HEVs in draining LNs and thereby exert “remote control” over the composition of leukocyte populations that home to these organs from the blood.

[1]  I. Charo,et al.  A Mechanism for the Impaired IFN-γ Production in C-C Chemokine Receptor 2 (CCR2) Knockout Mice: Role of CCR2 in Linking the Innate and Adaptive Immune Responses1 , 2000, The Journal of Immunology.

[2]  D. Jäger,et al.  The Leukotriene C4 Transporter MRP1 Regulates CCL19 (MIP-3β, ELC)–Dependent Mobilization of Dendritic Cells to Lymph Nodes , 2000, Cell.

[3]  Stephen Shaw,et al.  Lymph-Borne Chemokines and Other Low Molecular Weight Molecules Reach High Endothelial Venules via Specialized Conduits While a Functional Barrier Limits Access to the Lymphocyte Microenvironments in Lymph Node Cortex , 2000, The Journal of experimental medicine.

[4]  C. Mackay,et al.  T-cell function and migration. Two sides of the same coin. , 2000, The New England journal of medicine.

[5]  M. Bendeck.  Mining the myocardium with macrophage drills: A novel mechanism for revascularization. , 2000, Circulation research.

[6]  G. Cornelis,et al.  Molecular and cell biology aspects of plague. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[7]  J. Ward,et al.  Human endothelial cells express CCR2 and respond to MCP-1: direct role of MCP-1 in angiogenesis and tumor progression. , 2000, Blood.

[8]  A. Sher,et al.  Analysis of Fractalkine Receptor CX3CR1 Function by Targeted Deletion and Green Fluorescent Protein Reporter Gene Insertion , 2000, Molecular and Cellular Biology.

[9]  K. Yasukawa,et al.  Activity of interleukin 6 in the differentiation of monocytes to macrophages and dendritic cells , 2000, British journal of haematology.

[10]  M. Loda,et al.  Control of TH2 polarization by the chemokine monocyte chemoattractant protein-1 , 2000, Nature.

[11]  U. V. von Andrian,et al.  The Cc Chemokine Thymus-Derived Chemotactic Agent 4 (Tca-4, Secondary Lymphoid Tissue Chemokine, 6ckine, Exodus-2) Triggers Lymphocyte Function–Associated Antigen 1–Mediated Arrest of Rolling T Lymphocytes in Peripheral Lymph Node High Endothelial Venules , 2000, The Journal of experimental medicine.

[12]  R. Steinman,et al.  Differentiation of phagocytic monocytes into lymph node dendritic cells in vivo. , 1999, Immunity.

[13]  F. Luscinskas,et al.  MCP-1 and IL-8 trigger firm adhesion of monocytes to vascular endothelium under flow conditions , 1999, Nature.

[14]  L. Williams,et al.  Mice Lacking Expression of Secondary Lymphoid Organ Chemokine Have Defects in Lymphocyte Homing and Dendritic Cell Localization , 1999, The Journal of experimental medicine.

[15]  B. Rollins,et al.  Monocyte chemoattractant protein-1. , 1999, Chemical immunology.

[16]  R. Steinman,et al.  Differentiation of monocytes into dendritic cells in a model of transendothelial trafficking. , 1998, Science.

[17]  J. White,et al.  Macrophage-inflammatory protein-3 beta/EBI1-ligand chemokine/CK beta-11, a CC chemokine, is a chemoattractant with a specificity for macrophage progenitors among myeloid progenitor cells. , 1998, Journal of immunology.

[18]  R. Steinman,et al.  Dendritic cells and the control of immunity , 1998, Nature.

[19]  C. Martínez-A,et al.  Monocyte chemoattractant protein-1-induced CCR2B receptor desensitization mediated by the G protein-coupled receptor kinase 2. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[20]  H. Broxmeyer,et al.  CKβ-11/Macrophage Inflammatory Protein-3β/EBI1-Ligand Chemokine Is an Efficacious Chemoattractant for T and B Cells , 1998, The Journal of Immunology.

[21]  B. Rollins,et al.  Abnormalities in Monocyte Recruitment and Cytokine Expression in Monocyte Chemoattractant Protein 1–deficient Mice , 1998, The Journal of experimental medicine.

[22]  E. Butcher,et al.  Molecular Mechanisms of Lymphocyte Homing to Peripheral Lymph Nodes , 1998, The Journal of experimental medicine.

[23]  J. Cyster,et al.  A chemokine expressed in lymphoid high endothelial venules promotes the adhesion and chemotaxis of naive T lymphocytes. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[24]  R. Hannon,et al.  Endogenous monocyte chemoattractant protein‐1 recruits monocytes in the zymosan peritonitis model , 1998, Journal of leukocyte biology.

[25]  Robert V Farese,et al.  Impaired monocyte migration and reduced type 1 (Th1) cytokine responses in C-C chemokine receptor 2 knockout mice. , 1997, The Journal of clinical investigation.

[26]  P. Tsao,et al.  Anti-CD43 inhibits monocyte-endothelial adhesion in inflammation and atherogenesis. , 1997, Blood.

[27]  M. Auer,et al.  Transcytosis and Surface Presentation of IL-8 by Venular Endothelial Cells , 1997, Cell.

[28]  M. Ridanpää,et al.  Molecular Cloning of a Novel Human CC Chemokine Secondary Lymphoid-Tissue Chemokine That Is a Potent Chemoattractant for Lymphocytes and Mapped to Chromosome 9p13* , 1997, The Journal of Biological Chemistry.

[29]  C. Martínez-A,et al.  The amino-terminal domain of the CCR2 chemokine receptor acts as coreceptor for HIV-1 infection. , 1997, The Journal of clinical investigation.

[30]  Stephen Shaw,et al.  Cords, channels, corridors and conduits: critical architectural elements facilitating cell interactions in the lymph node cortex , 1997, Immunological reviews.

[31]  D. Connor.  Pathology of infectious diseases , 1997 .

[32]  T. Springer,et al.  Sequential regulation of alpha 4 beta 1 and alpha 5 beta 1 integrin avidity by CC chemokines in monocytes: implications for transendothelial chemotaxis , 1996, The Journal of cell biology.

[33]  Hub,et al.  Methods for Study of Chemokine Receptors in the Tissues , 1996, Methods.

[34]  L. Picker,et al.  Lymphocyte Homing and Homeostasis , 1996, Science.

[35]  T. Springer,et al.  The C–C Chemokine MCP-1 Differentially Modulates the Avidity of β1 and β2 Integrins on T Lymphocytes , 1996 .

[36]  T. Springer,et al.  Sequential Regulation of ct4131 and ct5131 Integrin Avidity by CC Chemokines in Monocytes: Implications for Transendothelial Chemotaxis , 1996 .

[37]  U. V. von Andrian.  Intravital microscopy of the peripheral lymph node microcirculation in mice. , 1996, Microcirculation.

[38]  G. Randolph,et al.  A soluble gradient of endogenous monocyte chemoattractant protein-1 promotes the transendothelial migration of monocytes in vitro. , 1995, Journal of immunology.

[39]  K. Ley,et al.  Lymphocyte homing and leukocyte rolling and migration are impaired in L-selectin-deficient mice. , 1994, Immunity.

[40]  F. Sallusto,et al.  Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha , 1994, The Journal of experimental medicine.

[41]  Cord Sunderkötter,et al.  Macrophages and angiogenesis , 1994, Journal of leukocyte biology.

[42]  T. Springer.  Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigm , 1994, Cell.

[43]  E. Butcher.  Leukocyte-endothelial cell recognition: Three (or more) steps to specificity and diversity , 1991, Cell.

[44]  P. Streeter,et al.  The influence of afferent lymphatic vessel interruption on vascular addressin expression , 1991, The Journal of cell biology.

[45]  A. Abbas,et al.  Histologic analysis of T lymphocyte activation in reactive lymph nodes. , 1991, Journal of immunology.

[46]  N. Van Rooijen,et al.  Elimination of spleen and of lymph node macrophages and its difference in the effect on the immune response to particulate antigens. , 1990, Immunobiology.

[47]  E. Butcher,et al.  Immunohistologic and functional characterization of a vascular addressin involved in lymphocyte homing into peripheral lymph nodes , 1988, The Journal of cell biology.

[48]  R. van Furth,et al.  Distribution of blood monocytes between a marginating and a circulating pool , 1986, The Journal of experimental medicine.

[49]  V. Perry,et al.  The mononuclear phagocyte system of the mouse defined by immunohistochemical localisation of antigen F4/80: macrophages associated with epithelia. , 1984, The Anatomical record.

[50]  D. Hume,et al.  The mononuclear phagocyte system of the mouse defined by immunohistochemical localization of antigen F4/80. Relationship between macrophages, Langerhans cells, reticular cells, and dendritic cells in lymphoid and hematopoietic organs , 1983, The Journal of experimental medicine.

[51]  I. Weissman,et al.  A cell-surface molecule involved in organ-specific homing of lymphocytes , 1983, Nature.

[52]  B. Hillman,et al.  Microvascular alterations in the lymph node during the BCG-induced immune response. , 1979, Lymphology.

[53]  V. Marchesi,et al.  The migration of lymphocytes through the endothelium of venules in lymph nodes: an electron microscope study , 1964, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[54]  V. Marchesi.  The site of leucocyte emigration during inflammation. , 1961, Quarterly journal of experimental physiology and cognate medical sciences.

[55]  W. Simpson,et al.  Plague , 2012, Nature.