Transendothelial migration of lymphocytes across high endothelial venules into lymph nodes is affected by metalloproteinases

Blood ◽  
2001 ◽  
Vol 98 (3) ◽  
pp. 688-695 ◽  
Author(s):  
Christelle Faveeuw ◽  
Graham Preece ◽  
Ann Ager
Keyword(s):  
Basement Membrane ◽  
Lymph Nodes ◽  
Transendothelial Migration ◽  
Basement Membranes ◽  
Lymphocyte Migration ◽  
Endothelial Lining ◽  
High Endothelial Venules ◽  
Mmp Inhibitor ◽  
Cell Lining

Abstract The migration of lymphocytes from the bloodstream into lymph nodes (LNs) via high endothelial venules (HEVs) is a prerequisite for the detection of processed antigen on mature dendritic cells and the initiation of immune responses. The capture and arrest of lymphocytes from flowing blood is mediated by the multistep adhesion cascade, but the mechanisms that lymphocytes use to penetrate the endothelial lining and the basement membrane of HEVs are poorly understood. Matrix metalloproteinases (MMPs) control the metastatic spread of tumor cells by regulating the penetration blood vessel basement membranes. In this study, synthetic and natural inhibitors were used to determine the role of MMPs and MMP-related enzymes in regulating lymphocyte extravasation in mice. Mice were treated systemically with the hydroxamate-based MMP inhibitor Ro 31-9790 and plasma monitored for effective levels of Ro 31-9790, which block shedding of L-selectin. The total numbers of lymphocytes recruited into LNs were not altered, but L-selectin levels were higher in mice treated with Ro 31-9790. A reduced number of lymphocytes completed diapedesis and there was an increase in the number of lymphocytes in the endothelial cell lining, rather than the lumen or the basement membrane of HEVs. Lymphocyte migration and L-selectin expression in the spleen were not altered by Ro 31-9790 treatment. Two MMP inhibitors, TIMP1 and Ro 32-1541, did not block L-selectin shedding and had no effect on lymphocyte migration across HEVs. These results suggest that metalloproteinase activity is required for lymphocyte transmigration across HEVs into LNs and provide evidence for the concept that metalloproteinases are important players in some forms of transendothelial migration.

Role of fenestrated basement membrane in lymphatic absorption from peritoneal cavity

1959 ◽  
Vol 197 (3) ◽  
pp. 551-554 ◽  
Author(s):  
Lane Allen ◽  
Tim Weatherford
Keyword(s):  
Basement Membrane ◽  
Lymph Nodes ◽  
Peritoneal Cavity ◽  
Intraperitoneal Injection ◽  
Entire Population ◽  
Polystyrene Spheres ◽  
Lymphatic Absorption ◽  
Regional Lymph Nodes ◽  
Histological Picture

Polystyrene spheres with a range from chylomicron size up to 30 µ were injected into the peritoneal cavity of mouse, rat and cat, and were recovered from the regional lymph nodes. The largest recovered spheres in the mouse were 16.8 µ in diameter, in the rat and cat 24 µ. Inspection of the entire population of spheres recovered from lymph nodes 48 hours after intraperitoneal injection indicated that most of the fenestrations in the subperitoneal basement membrane are less than 5 µ in the mouse, and more than 5 µ in the cat. Fenestrations in the rat are intermediate between mouse and cat. The deductions as to fenestrations from inspection of the absorbed sphere populations is fairly well in accord with the histological picture in the mouse and cat. Many spheres reach the circulation and the larger ones are filtered out in the lungs, with resulting atelectasis.

scholarly journals Regulation of the differentiation and behaviour of extra-embryonic endodermal cells by basement membranes

2001 ◽  
Vol 114 (5) ◽  
pp. 931-939 ◽  
Author(s):  
P. Murray ◽  
D. Edgar
Keyword(s):  
Stem Cells ◽  
Basement Membrane ◽  
Embryonic Stem ◽  
Basement Membranes ◽  
Embryoid Bodies ◽  
Endodermal Differentiation ◽  
And Migration ◽  
The Individual ◽  
Endodermal Cells

Both the extracellular matrix and parathyroid hormone-related peptide (PTHrP) have been implicated in the differentiation and migration of extra-embryonic endodermal cells in the pre-implantation mammalian blastocyst. In order to define the individual roles and interactions between these factors in endodermal differentiation, we have used embryoid bodies derived from Lamc1(-/-) embryonic stem cells that lack basement membranes. The results show that in the absence of basement membranes, increased numbers of both visceral and parietal endodermal cells differentiate, but they fail to form organised epithelia. Furthermore, although parietal endodermal cells only migrate away from control embryoid bodies in the presence of PTHrP, they readily migrate from Lamc1(-/-) embryoid bodies in the absence of PTHrP, and this migration is unaffected by PTHrP. Thus, the basement membrane between epiblast and extra-embryonic endoderm is required for the proper organisation of visceral and parietal endodermal cells and also restricts their differentiation to maintain the population of primitive endodermal stem cells. Moreover, this basement membrane inhibits migration of parietal endodermal cells, the role of PTHrP being to stimulate delamination of parietal endodermal cells from the basement membrane rather than promoting migration per se.

scholarly journals The Route of Antigen Entry Determines the Requirement for L-selectin during Immune Responses

1996 ◽  
Vol 184 (6) ◽  
pp. 2341-2352 ◽  
Author(s):  
Michelle D. Catalina ◽  
Michael C. Carroll ◽  
Helen Arizpe ◽  
Akira Takashima ◽  
Pila Estess ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Nodes ◽  
Contact Hypersensitivity ◽  
Targeted Disruption ◽  
High Endothelial Venules ◽  
Peripheral Lymph ◽  
Successful Execution ◽  
Alternate Routes ◽  
Deficient Mice

L-selectin, an adhesion molecule constitutively expressed on leukocytes, is important for primary adhesion and extravasation of lymphocytes at specialized high endothelial venules within lymph nodes and other leukocytes at sites of inflammation. We have generated L-selectin–deficient mice by targeted disruption, and have confirmed a previously reported phenotype which includes strikingly impaired contact hypersensitivity (CHS) responses to reactive haptens (Tedder, T.F., D.A. Steeber, and P. Pizcueta. 1995. J. Exp. Med. 181:2259–2264; Xu, J.C., I.S. Grewal, G.P. Geba, and R.A. Flavell. 1996. 183:589–598.). Since the mechanism of this impairment has not been clarified, we sought to define the stage(s) at which the CHS response is affected in L-selectin–deficient mice. We show that epidermal Langerhans cells in L-selectin– deficient mice are normal in number, migrate to peripheral lymph nodes appropriately, and are functional in presenting allogeneic and haptenic antigens. Moreover, T cells, as well as neutrophil and monocyte effector populations, are fully capable of entry into the inflamed skin sites in the absence of L-selectin. Thus, antigen presentation and effector mechanisms are intact in L-selectin deficient mice. In contrast, virtually no antigen-specific T cells can be found within draining peripheral nodes after a contact challenge, suggesting that the defect resides primarily in the inability of antigen-specific T cells to home to and be activated in these nodes. Indeed, L-selectin–deficient mice mount completely normal CHS responses when alternate routes of immunization are used. These studies pinpoint the lesion in CHS to a discrete stage of the afferent limb of the response, clarify the role of L-selectin on effector populations, and illustrate the critical importance of the route of antigen entry to the successful execution of an immune response.

scholarly journals The Absence of Nidogen 1 Does Not Affect Murine Basement Membrane Formation

2000 ◽  
Vol 20 (18) ◽  
pp. 7007-7012 ◽  
Author(s):  
Monzur Murshed ◽  
Neil Smyth ◽  
Nicolai Miosge ◽  
Jörg Karolat ◽  
Thomas Krieg ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Embryonic Stem ◽  
Collagen Iv ◽  
Basement Membranes ◽  
Null Mutation ◽  
Membrane Structures ◽  
Membrane Formation ◽  
Nidogen 1

ABSTRACT Nidogen 1 is a highly conserved protein in mammals,Drosophila melanogaster, Caenorhabditis elegans, and ascidians and is found in all basement membranes. It has been proposed that nidogen 1 connects the laminin and collagen IV networks, so stabilizing the basement membrane, and integrates other proteins, including perlecan, into the basement membrane. To define the role of nidogen 1 in basement membranes in vivo, we produced a null mutation of the NID-1 gene in embryonic stem cells and used these to derive mouse lines. Homozygous animals produce neither nidogen 1 mRNA nor protein. Surprisingly, they show no overt abnormalities and are fertile, their basement membrane structures appearing normal. Nidogen 2 staining is increased in certain basement membranes, where it is normally only found in scant amounts. This occurs by either redistribution from other extracellular matrices or unmasking of nidogen 2 epitopes, as its production does not appear to be upregulated. The results show that nidogen 1 is not required for basement membrane formation or maintenance.

The chemokine receptor CCR7 and α4 integrin are important for migration of chronic lymphocytic leukemia cells into lymph nodes

Blood ◽  
2002 ◽  
Vol 99 (8) ◽  
pp. 2977-2984 ◽  
Author(s):  
Kathleen J. Till ◽  
Ke Lin ◽  
Mirko Zuzel ◽  
John C. Cawley
Keyword(s):  
Lymph Node ◽  
Chronic Lymphocytic Leukemia ◽  
Lymph Nodes ◽  
Lymph Node Involvement ◽  
Lymphocytic Leukemia ◽  
Lymphocyte Migration ◽  
High Endothelial Venules ◽  
Lymph Node Enlargement ◽  
Node Involvement

Abstract Malignant lymphocyte migration into lymph nodes is an important aspect of chronic lymphocytic leukemia (CLL), yet little is known about the processes involved. Here we demonstrate that CLL cells migrate across vascular endothelium in response to at least 3 chemokines, namely, CCL21, CCL19, and CXCL12. Moreover, transendothelial cell migration (TEM) in response to CCL21 and CCL19 was significantly higher for the malignant B cells of patients who had clinical lymph node involvement as compared with those of patients lacking such organomegaly. Furthermore, the expression of CCR7, the receptor for both CCL21 and CCL19, correlated with clinical lymphadenopathy, and blocking of CCR7 inhibited CLL cell TEM. By using immunohistochemistry we demonstrated that CCL21 and CCL19, but not CXCL12, are located in high endothelial venules and are, therefore, in an appropriate location to induce TEM. Regarding the adhesion receptors involved in TEM, α4 (most likely in association with β1) and αLβ2 were shown to be important in CLL cell TEM in vitro, but only the level of α4 expression correlated with the presence of clinical lymphadenopathy. The present studies are the first to shed light on the factors determining CLL cell entry into nodes and define the phenotype of circulating malignant cells likely to determine the pattern of lymph node enlargement in the disease.

scholarly journals A Novel Migration Pathway for Rat Dendritic Cells from the Blood: Hepatic Sinusoids–Lymph Translocation

1997 ◽  
Vol 185 (4) ◽  
pp. 777-784 ◽  
Author(s):  
Shunsuke Kudo ◽  
Kenjiro Matsuno ◽  
Taichi Ezaki ◽  
Michio Ogawa
Keyword(s):  
Dendritic Cells ◽  
Lymph Nodes ◽  
Kupffer Cells ◽  
Lymphoid Tissues ◽  
Proliferating Cells ◽  
High Endothelial Venules ◽  
Regional Lymph Nodes ◽  
Migration Pathway ◽  
Migration Pathways

The migration pathways for dendritic cells (DC) from the blood are not yet completely resolved. In our previous study, a selective recruitment of DC progenitors from the blood to the liver was suggested. To clarify the role of the hepatic sinusoids in the migration of blood DC, relatively immature DC and mature DC were isolated from hepatic and intestinal lymph, and intravenously transferred to allogeneic hosts. It was then possible to detect small numbers of DC within secondary lymphoid tissues either by immunostaining for donor type major histocompatibility complex class I antigen or, at much higher sensitivity, for bromodeoxyuridine incorporated by proliferating cells (mainly T lymphocytes), which responded to the alloantigen presented by the administered DC. The intravenously injected DC accumulated in the paracortex of regional lymph nodes of the liver via a lymph-borne pathway. Intravenously injected fluorochrome-labeled syngeneic DC behaved similarly. In contrast, very few DC were found in spleen sections and were hardly detectable in other lymph nodes or in other tissues. An in situ cell binding assay revealed a significant and selective binding of DC to Kupffer cells in liver cryosections. It is concluded that rat DC can undergo a blood–lymph translocation via the hepatic sinusoids, but not via the high endothelial venules of lymph nodes. Hence the hepatic sinusoids may act as a biological concentrator of blood DC into the regional hepatic nodes. Kupffer cells may play an important role in this mechanism.

Importance of nidogen binding to laminin gamma1 for branching epithelial morphogenesis of the submandibular gland

Development ◽  
1997 ◽  
Vol 124 (3) ◽  
pp. 683-691 ◽  
Author(s):  
Y. Kadoya ◽  
K. Salmivirta ◽  
J.F. Talts ◽  
K. Kadoya ◽  
U. Mayer ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Submandibular Gland ◽  
Driving Forces ◽  
Basement Membranes ◽  
Epithelial Morphogenesis ◽  
Epidermal Growth ◽  
Membrane Components ◽  
Blocking Antibodies

Epithelial-mesenchymal interactions are major driving forces for the development of most solid organs. The importance of these interactions was first shown for the embryonic submandibular gland more than 40 years ago. We here present evidence that interactions between two basement membrane components, nidogen (entactin) and laminin gamma1 chain, could be important for epithelial-mesenchymal interactions in this gland. Nidogen mRNA was detected by in situ hybridization in the mesenchyme, and yet the protein was detected in epithelial and endothelial basement membranes. The role of nidogen-laminin interactions for epithelial morphogenesis was studied by applying antibodies to submandibular gland organ cultures. Antibodies reacting strongly with the nidogen-binding site of laminin gamma1 chain drastically perturbed branching epithelial morphogenesis. Electron microscopy of the epithelial-mesenchymal interface showed that blocking antibodies disrupted the formation of the basement membrane. Epidermal growth factor was shown to increase the expression of nidogen in mesenchyme, and could counteract the effect of the blocking antibodies. We suggest that nidogen could be an important mesenchymal factor for submandibular gland development.

Enhanced assembly of basement membrane matrix by endodermal cells in response to fibronectin substrata

1991 ◽  
Vol 99 (2) ◽  
pp. 443-451
Author(s):  
M.R. Austria ◽  
J.R. Couchman
Keyword(s):  
Extracellular Matrix ◽  
Basement Membrane ◽  
Basement Membranes ◽  
Binding Domain ◽  
Type I ◽  
Matrix Assembly ◽  
Matrix Deposition ◽  
Membrane Matrix ◽  
The Matrix

Basement membranes are complex extracellular matrices contributing to the regulation of growth, migration and differentiation of many cell types. However, little is known about the mechanisms regulating the deposition and assembly of basement membrane from its constituents. We have investigated the role of extracellular matrix molecules in the control of basement membrane matrix assembly by cultured endodermal (PFHR-9) cells. In the presence of fibronectin-depleted serum, substrata of fibronectin or laminin induced an increase in deposition of laminin, type IV collagen and proteoglycans by PFHR-9 cells, in comparison to cells adherent to type I collagen-coated, vitronectin-coated or uncoated substrata. Direct effects of fibronectin or laminin on the degree of cell spreading or rate of proliferation were not responsible for enhanced matrix deposition. The effect did not result from a redirection of basement membrane components to the matrix, since there was no decrease in matrix constituents released to the culture supernatants. Furthermore, the synthesis and release of other molecules that are not basement membrane constituents was unaltered in response to different extracellular matrix substrata. Experiments with fibronectin fragments showed that a 105 × 10(3) Mr ‘cell’-binding domain (containing the cell attachment sequence Arg-Gly-Asp-Ser) was an important contributor to enhanced matrix deposition, while the N-terminal 29 × 10(3) Mr heparin-binding domain also contributed to the effect, particularly with respect to heparan sulfate proteoglycan deposition. It seems that fibronectin has a dual role of action in promoting basement membrane matrix assembly, through direct cell surface interactions, and through the binding of fibronectin to other matrix components that may nucleate or stabilize the matrix assembly.

Sign in / Sign up

Export Citation Format

Share Document