Structure and function of rat lymph nodes

Ohtani, Osamu; Ohtani, Yusuke

doi:10.1679/aohc.71.69

Cited by 85 publications

(68 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This reconstruction demonstrated the presence of multiple blunt-ended sinuses that started near HEVs in interfollicular regions or at the follicle/T-zone boundary (Fig. 1), in agreement with previous studies (12,13). Several connecting sinuses that extended from the subcapsular sinus (SCS) to medullary sinuses were also identified and usually were located adjacent to a B-cell follicle as well as passing near HEVs ( Fig.…”

Section: Resultssupporting

confidence: 90%

“…Using intravital twophoton laser scanning microscopy (TPLSM), it was shown that intrinsic expression of S1P 1 on T lymphocytes regulates their access into the cortical sinuses, whereas fluid flow within these sinuses mediates their retention and passive transport toward the medulla and efferent lymphatic (7). However, cortical sinuses often appear packed with cells (6,(9)(10)(11)(12) and it has been unclear whether all of these structures exhibit fluid flow.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Lymph node cortical sinus organization and relationship to lymphocyte egress dynamics and antigen exposure

Grigorova

Panteleev

Cyster

2010

Proc. Natl. Acad. Sci. U.S.A.

141

137

View full text Add to dashboard Cite

Recent studies have identified cortical sinuses as sites of sphingosine-1-phosphate receptor-1 (S1P 1 )-dependent T-and B-cell egress from the lymph node (LN) parenchyma. However, the distribution of cortical sinuses in the entire LN and the extent of lymph flow within them has been unclear. Using 3D reconstruction and intravital two-photon microscopy we describe the branched organization of the cortical sinus network within the inguinal LN and show that lymphocyte flow begins within blunt-ended sinuses. Many cortical sinuses are situated adjacent to high endothelial venules, and some lymphocytes access these sinuses within minutes of entering a LN. However, upon entry to inflamed LNs, lymphocytes rapidly up-regulate CD69 and are prevented from accessing cortical sinuses. Using the LN reconstruction data and knowledge of lymphocyte migration and cortical sinus entry dynamics, we developed a mathematical model of T-cell egress from LNs. The model suggests that random walk encounters with lymphatic sinuses are the major factor contributing to LN transit times. A slight discrepancy between predictions of the model and the measured transit times may be explained by lymphocytes undergoing a few rounds of migration between the parenchyma and sinuses before departing from the LN. Because large soluble antigens gain rapid access to cortical sinuses, such parenchyma-sinus shuttling may facilitate antibody responses.ymphocyte recirculation between blood, lymphoid organs, and lymph is essential for immune surveillance. T and B lymphocytes get into LNs from the blood through high endothelial venules (HEVs); they then move into the T zone and B-cell follicles, respectively, and migrate there in a stromally guided random walk. If no antigenic stimuli have been encountered, lymphocytes leave into the efferent lymphatics after a characteristic residence time in murine lymph nodes (LNs) of 6-10 h for T cells and 12-24 h for B cells (1-3). During some immune responses, egress of naive lymphocytes from LNs is transiently blocked by IFNα/β. This egress "shutdown" has been modeled by systemic treatment with double-stranded mRNA mimetic polyinosine-polycytidylic acid [poly(I:C)] that induces secretion of IFNα/β, as well as with lymphocytic choriomeningitis virus (LCMV) infection (4). The induced block in egress partially depends on lymphocyte-intrinsic up-regulation of CD69. CD69 is a transmembrane protein that negatively regulates sphingosine-1-phosphate receptor-1 (S1P 1 ), a receptor for sphingosine-1-phosphate (S1P) that is required for lymphocyte egress (4, 5). However, the stage at which CD69 inhibits cell departure from the LNs has not been fully defined.Recent studies of murine LNs identified lymphatic vascular endothelial gene-1 (LYVE-1) + cortical sinuses as sites of T-and B-cell exit from the LN parenchyma (6-8). Using intravital twophoton laser scanning microscopy (TPLSM), it was shown that intrinsic expression of S1P 1 on T lymphocytes regulates their access into the cortical sinuses, whereas fluid flow within these sinu...

show abstract

Section: Resultssupporting

confidence: 90%

mentioning

confidence: 99%

Lymph node cortical sinus organization and relationship to lymphocyte egress dynamics and antigen exposure

Grigorova

Panteleev

Cyster

2010

Proc. Natl. Acad. Sci. U.S.A.

141

137

View full text Add to dashboard Cite

show abstract

“…PH lymphatic vessels expressing aquaporin 1 ( Figure 2) were evident, as were vascular cell adhesion molecule-positive ( Figure 2) high endothelial venules. Aquaporin 1 1 and vascular cell adhesion molecule were expressed by high endothelial venule endothelium and by cells lining sinuses consistent with previous localizations (18). Antibodies against peripheral node addressin (PNAd) did not distinguish BALT structures or cellular constituents above background in rat lungs (not shown).…”

Section: Balts In Ph Lung Are Well Vascularized and Selectively Adhesivesupporting

confidence: 88%

Bronchus-associated Lymphoid Tissue in Pulmonary Hypertension Produces Pathologic Autoantibodies

Colvin¹,

Cripe²,

Ivy³

et al. 2013

Am J Respir Crit Care Med

View full text Add to dashboard Cite

Rationale: Autoimmunity has long been associated with pulmonary hypertension. Bronchus-associated lymphoid tissue plays important roles in antigen sampling and self-tolerance during infection and inflammation. Objectives: We reasoned that activated bronchus-associated lymphoid tissue would be evident in rats with pulmonary hypertension, and that loss of self-tolerance would result in production of pathologic autoantibodies that drive vascular remodeling. Methods: We used animal models, histology, and gene expression assays to evaluate the role of bronchus-associated lymphoid tissue in pulmonary hypertension. Measurements and Main Results: Bronchus-associated lymphoid tissue was more numerous, larger, and more active in pulmonary hypertension compared with control animals. We found dendritic cells in and around lymphoid tissue, which were composed of CD31 T cells over a core of CD45RA 1 B cells. Antirat IgG and plasma from rats with pulmonary hypertension decorated B cells in lymphoid tissue, resistance vessels, and adventitia of large vessels. Lymphoid tissue in diseased rats was vascularized by aquaporin-1 1 high endothelial venules and vascular cell adhesion molecule-positive vessels. Autoantibodies are produced in bronchus-associated lymphoid tissue and, when bound to pulmonary adventitial fibroblasts, change their phenotype to one that may promote inflammation. Passive transfer of autoantibodies into rats caused pulmonary vascular remodeling and pulmonary hypertension. Diminution of lymphoid tissue reversed pulmonary hypertension, whereas immunologic blockade of CCR7 worsened pulmonary hypertension and hastened its onset. Conclusions: Bronchus-associated lymphoid tissue expands in pulmonary hypertension and is autoimmunologically active. Loss of self-tolerance contributes to pulmonary vascular remodeling and pulmonary hypertension. Lymphoid tissue-directed therapies may be beneficial in treating pulmonary hypertension.Keywords: hypertension; pulmonary; lymphoid tissue; inflammation; autoimmunity Pulmonary hypertension (PH) is characterized by progressive increases in pulmonary artery pressure and pulmonary vascular resistance resulting in right ventricular failure (1). The primary histopathologic finding in PH is vascular remodeling, in which the pulmonary vasculature becomes stiff, occluded, and fibrotic (2). Vascular remodeling seems to require lung infiltration of inflammatory cells, and continual influx likely sustains a cycle of perpetual inflammation and remodeling by poorly defined mechanisms (3).The bronchovascular space is a structure that marries sterile (vasculature) and nonsterile (airway) components. Bronchusassociated lymphoid tissues (BALTs) are tertiary lymphoid organs that provide an elegant immune surveillance apparatus ensuring airway and vessel homeostatic patency. They are histologically similar to lymph nodes containing afferent lymphatic connection, B cells, T cells, antigen-presenting cells, stroma, and a vascular supply (4). The chief antigen-presenting cells in BALT are dendritic ce...

show abstract

“…We will briefly discuss the structure of the initial part of the lymph system based on several more extensive reviews (336,414), adhering to the terminology of SchmidSchönbein (414).…”

Section: Structural Properties Of Lymphatic Capillariesmentioning

confidence: 99%

Interstitial Fluid and Lymph Formation and Transport: Physiological Regulation and Roles in Inflammation and Cancer

Wiig

Swartz²

2012

Physiological Reviews

577

574

View full text Add to dashboard Cite

The interstitium describes the fluid, proteins, solutes, and the extracellular matrix (ECM) that comprise the cellular microenvironment in tissues. Its alterations are fundamental to changes in cell function in inflammation, pathogenesis, and cancer. Interstitial fluid (IF) is created by transcapillary filtration and cleared by lymphatic vessels. Herein we discuss the biophysical, biomechanical, and functional implications of IF in normal and pathological tissue states from both fluid balance and cell function perspectives. We also discuss analysis methods to access IF, which enables quantification of the cellular microenvironment; such methods have demonstrated, for example, that there can be dramatic gradients from tissue to plasma during inflammation and that tumor IF is hypoxic and acidic compared with subcutaneous IF and plasma. Accumulated recent data show that IF and its convection through the interstitium and delivery to the lymph nodes have many and diverse biological effects, including in ECM reorganization, cell migration, and capillary morphogenesis as well as in immunity and peripheral tolerance. This review integrates the biophysical, biomechanical, and biological aspects of interstitial and lymph fluid and its transport in tissue physiology, pathophysiology, and immune regulation.

show abstract

Structure and function of rat lymph nodes

Cited by 85 publications

References 20 publications

Lymph node cortical sinus organization and relationship to lymphocyte egress dynamics and antigen exposure

Lymph node cortical sinus organization and relationship to lymphocyte egress dynamics and antigen exposure

Bronchus-associated Lymphoid Tissue in Pulmonary Hypertension Produces Pathologic Autoantibodies

Interstitial Fluid and Lymph Formation and Transport: Physiological Regulation and Roles in Inflammation and Cancer

Contact Info

Product

Resources

About