scholarly journals Cell Migration in the Immune System: the Evolving Inter-Related Roles of Adhesion Molecules and Proteinases

2000 ◽  
Vol 7 (2-4) ◽  
pp. 103-116 ◽  
Author(s):  
Joseph A. Madri ◽  
Donnasue Graesser
Keyword(s):  
Endothelial Cells ◽  
Cell Migration ◽  
Matrix Metalloproteinases ◽  
Basement Membrane ◽  
Leukocyte Adhesion ◽  
Therapeutic Approaches ◽  
Adhesion Receptors ◽  
Extracellular Matrix Components ◽  
Membrane Bound ◽  
Tissue Site

Leukocyte extravasation into perivascular tissue during inflammation and lymphocyte homing to lymphoid organs involve transient adhesion to the vessel endothelium, followed by transmigration through the endothelial cell (EC) layer and establishment of residency at the tissue site for a period of time. In these processes, leukocytes undergo multiple attachments to, and detachments from, the vessel-lining endothelial cells, prior to transendothelial cell migration. Transmigrating leukocytes must traverse a subendothelial basement membrane en route to perivascular tissues and utilize enzymes known as matrix metalloproteinases to make selective clips in the extracellular matrix components of the basement membrane. This review will focus on the evidence for a link between adhesion of leukocytes to endothelial cells, the induction of matrix metalloproteinases mediated by engagement of adhesion receptors on leukocytes, and the ability to utilize these matrix metalloproteinases to facilitate leukocyte invasion of tissues. Leukocytes with invasive phenotypes express high levels of MMPs, and expression of MMPs enhances the migratory and invasive properties of these cells. Furthermore, MMPs may be used by lymphocytes to proteolytically cleave molecules such as adhesion receptors and membrane bound cytokines, increasing their efficiency in the immune response. Engagement of leukocyte adhesion receptors may modulate adhesive (modulation of integrin affinities and expression), synthetic (proteinase induction and activation), and surface organization (clustering of proteolyric complexes) behaviors of invasive leukocytes. Elucidation of these pathways will lead to better understanding of controlling mechanisms in order to develop rational therapeutic approaches in the areas of inflammation and autoimmunity.

The Relevance of Blood Cell-Vessel Wall Adhesive Interactions for Vascular Thrombotic Disease

1999 ◽  
Vol 82 (08) ◽  
pp. 962-970 ◽  
Author(s):  
Andreas May ◽  
Franz-Josef Neumann ◽  
Klaus Preissner
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Adhesion Molecules ◽  
Vessel Wall ◽  
Leukocyte Adhesion ◽  
Factor Vii ◽  
Sialyl Lewisx ◽  
Thrombotic Disease ◽  
Cellular Expression ◽  
Extracellular Matrix Components

IntroductionFollowing an inflammatory or infectious stimulus, the body’s defense mechanism initiates recruitment of circulating leukocytes toward the inflammatory stimulus. The emigration of leukocytes into extravascular tissues occurs in a highly coordinated fashion in multiple steps, including rolling and tethering of blood cells along the vascular endothelium and their firm attachment and subsequent transmigration and invasion toward the inflammatory site.1 During these sequential steps, transcellular recognition of different adhesion receptor/counterligand pairs, such as selectins/sialyl LewisX-carbohydrates,2 integrins/ immunoglobulin superfamily cell adhesion molecules (ICAMs),3 or binding to (provisional) extracellular matrix components, such as fibrinogen/fibrin, vitronectin, or fibronectin, control the strength and duration of interactions between leukocytes (neutrophils [polymorphonucleocytes (PMN)], eosinophils, monocytes and macrophages, mast cells, lymphocytes) and the vessel wall.4 The importance of these cellular interactions is evident from patients with the rare congenital disorders of “leukocyte-adhesion-deficiency,” which are either caused by a lack or dysfunction of ß2-integrins (LAD I) or a deficiency in the expression of sialyl-LewisX carbohydrates (LAD II).5 The interdependent adhesion processes are regulated by vascular cell-derived chemokines and chemoattractants that may directly influence the expression profile and activation state of adhesion molecules, such as ß2- and ß1-integrins, the shedding of selectins, and the nonthrombogenic properties of endothelial cells.6 Prior to transmigration, leukocyte adhesion may induce the disruption of vascular endothelial (VE)-cadherin mediated endothelial cell-to-cell junctions7 involving the proteasome machinery.8 The spatio-temporal cellular expression of juxtacrine adhesion and signaling receptors–particularly on PMN, endothelial cells, and platelets–contribute to the coordination of adhesion and inflammatory mechanisms required for vascular homeostasis9 and prothrombotic outcome under imbalanced conditions. Not only do monocytes express tissue factor (a receptor for the protease factor VII/VIIa) on their surface after stimulation with endotoxin or cytokines, but PMN contain cell surface receptors, such as the factor X/Xa-binding ß2-integrin Mac-1 or effector cell protease receptor (EPR)-1, that link cellular activation and inflammation with the induction of the blood clotting cascade and serve as an alternate pathway for thrombin formation.10,11 Moreover, defects in natural anticoagulant mechanisms, such as the thrombomodulin/protein C pathway, are potential risk factors for vascular thrombotic complications, as in myocardial infarction.12 Pathophysiological stimuli, such as dysregulated direct (i.e., adhesive contact) or indirect (i.e., release of soluble factors) activation of leukocytes, serious infectious agonists, or autoantibodies, may result in endothelial cell dysfunction or injury with the amplification of inflammatory and prothrombotic responses. In the following, some of the principal juxtacrine interactions between leukocytes, platelets, and endothelium, together with their direct or indirect influence on hemostasis and consequences for vascular thrombotic disease, will be discussed. Further understanding of the bidirectional cross-talk of adhesion receptors and the contribution of connecting points, such as protease receptors, may lead to promising therapeutic strategies that aim to protect or regain the endothelial defense mechanisms.

Cell-surface association between matrix metalloproteinases and integrins: role of the complexes in leukocyte migration and cancer progression

Blood ◽  
2006 ◽  
Vol 108 (5) ◽  
pp. 1441-1450 ◽  
Author(s):  
Michael Stefanidakis ◽  
Erkki Koivunen
Keyword(s):  
Cell Migration ◽  
Matrix Metalloproteinases ◽  
Cell Surface ◽  
Cancer Progression ◽  
Broad Spectrum ◽  
Leukocyte Adhesion ◽  
Leukocyte Migration ◽  
Β2 Integrins ◽  
Normal Leukocyte

Leukocyte motility is known to be dependent on both β2-integrins and matrix metalloproteinases MMP-2/-9 or gelatinases, which mediate leukocyte adhesion and the proteolysis needed for invasion, respectively. Gelatinases not only play an important role in cell migration, tissue remodeling, and angiogenesis during development, but are also involved in the progression and invasiveness of many cancers, including leukemias. The concept that MMPs associate with integrins, as well as their importance in some physiologic and pathologic conditions, has been advanced previously but has not been examined on leukocytes. This review will examine mainly the function of the MMP-integrin complexes in normal leukocyte migration and the effect of integrin and broad-spectrum MMP inhibitors in tumor progression.

New Discoveries with Mice Mutant in Endothelial and Platelet Selectins

1999 ◽  
Vol 82 (08) ◽  
pp. 850-857 ◽  
Author(s):  
Daqing Hartwell ◽  
Denisa Wagner
Keyword(s):  
Endothelial Cells ◽  
Cell Surface ◽  
Leukocyte Adhesion ◽  
Genetically Engineered ◽  
Immunoglobulin Superfamily ◽  
Adhesion Receptors ◽  
Pathological Conditions ◽  
Activated Platelets ◽  
Alternative Approach ◽  
Selectin Family

IntroductionThe selectin family of adhesion receptors consists of three members: P-, E-, and L-selectin. P-selectin is constitutively present in the α-granules of platelets and Weibel-Palade bodies of endothelial cells and is rapidly translocated to the cell surface upon activation. E-selectin is synthesized and expressed by activated endothelial cells, whereas L-selectin is constitutively expressed by leukocytes. All three selectins support the rolling of leukocytes on endothelium, which is a prerequisite to firm adhesion and extravasation of leukocytes mediated by integrins and members of the immunoglobulin superfamily.1,2 More recently, it has been demonstrated that P- and E-selectin also support platelet rolling in venules, which will be discussed below. In addition, P-selectin expressed on the surface of activated platelets also mediates platelet-leukocyte adhesion.3,4 Since the discovery of the selectins, considerable efforts have been devoted to uncover the functions of these molecules. The development of genetically engineered animals deficient in one or more of the adhesion receptors has provided a unique opportunity and an alternative approach to antibody-blocking experiments for defining the contribution of each of the molecules in normal physiology and pathological conditions. At this time, mice deficient in a single selectin, all combinations of two of the selectins, and all three selectins have been produced by gene targeting.5-10 In this chapter, we will discuss some of the recent findings obtained using mice deficient in P-selectin alone (P-/-), both P- and E-selectin (P/E-/-), and mice expressing Pselectin with a deleted cytoplasmic domain (ΔCT).

Platelets and matrix metalloproteinases

2013 ◽  
Vol 110 (11) ◽  
pp. 903-909 ◽  
Author(s):  
Peter Seizer ◽  
Andreas E. May
Keyword(s):  
Endothelial Cells ◽  
Cell Migration ◽  
Matrix Metalloproteinases ◽  
Vascular Injury ◽  
Tumour Cells ◽  
Leukocyte Recruitment ◽  
Receptor Interaction ◽  
Tissue Inhibitors ◽  
Tissue Inhibitors Of Metalloproteinase ◽  
Tissue Degradation

SummaryMatrix metalloproteinases (MMPs) and their inhibitors essentially contribute to a variety of pathophysiologies by modulating cell migration, tissue degradation and inflammation. Platelet-associated MMP activity appears to play a major role in these processes. First, platelets can concentrate leukocyte-derived MMP activity to sites of vascular injury by leukocyte recruitment. Second, platelets stimulate MMP production in e.g. leukocytes, endothelial cells, or tumour cells by direct receptor interaction or/and by paracrine pathways. Third, platelets synthesise and secrete a variety of MMPs including MMP-1, MMP-2, MMP-3, and MMP-14 (MT1-MMP), and potentially MMP-9 as well as the tissue inhibitors of metalloproteinase (TIMPs). This review focuses on platelet-derived and platelet-induced MMPs and their inhibitors.

Endothelial cell regulation of matrix metalloproteinases

2005 ◽  
Vol 83 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Tara L Haas
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Matrix Metalloproteinases ◽  
Basement Membrane ◽  
Matrix Proteins ◽  
Regulation Of Transcription ◽  
Cell Type ◽  
Sprouting Angiogenesis

The process of sprouting angiogenesis requires that the endothelial cells degrade the basement membrane matrix and migrate into the interstitial matrix. Matrix metalloproteinases are enzymes capable of cleaving numerous extracellular matrix proteins. Increased production and activity of matrix metalloproteinases in any cell type is associated with a more migratory and invasive phenotype. This paper describes results of recent in-vitro studies of the regulation of transcription and activation of MMP-2 and MT1-MMP in endothelial cells, as well as studies that examined roles of matrix metalloproteinases in activity-induced angiogenesis.Key words: proteolysis, extracellular matrix, angiogenesis, mechanotransduction.

scholarly journals Emerging Technologies to Study the Glomerular Filtration Barrier

2021 ◽  
Vol 8 ◽  
Author(s):  
Emma Gong ◽  
Laura Perin ◽  
Stefano Da Sacco ◽  
Sargis Sedrakyan
Keyword(s):  
Endothelial Cells ◽  
Kidney Disease ◽  
Basement Membrane ◽  
Therapeutic Approaches ◽  
Glomerular Filtration Barrier ◽  
Glomerular Function ◽  
Filtration Barrier ◽  
Single Cell Rna Sequencing ◽  
Kidney Organoids

Kidney disease is characterized by loss of glomerular function with clinical manifestation of proteinuria. Identifying the cellular and molecular changes that lead to loss of protein in the urine is challenging due to the complexity of the filtration barrier, constituted by podocytes, glomerular endothelial cells, and glomerular basement membrane. In this review, we will discuss how technologies like single cell RNA sequencing and bioinformatics-based spatial transcriptomics, as well as in vitro systems like kidney organoids and the glomerulus-on-a-chip, have contributed to our understanding of glomerular pathophysiology. Knowledge gained from these studies will contribute toward the development of personalized therapeutic approaches for patients affected by proteinuric diseases.

scholarly journals Pericytes support neutrophil subendothelial cell crawling and breaching of venular walls in vivo

2012 ◽  
Vol 209 (6) ◽  
pp. 1219-1234 ◽  
Author(s):  
Doris Proebstl ◽  
Mathieu-Benoît Voisin ◽  
Abigail Woodfin ◽  
James Whiteford ◽  
Fulvio D’Acquisto ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Endothelial Cells ◽  
Basement Membrane ◽  
Leukocyte Adhesion ◽  
Shape Change ◽  
Direct Analysis ◽  
Leukocyte Trafficking ◽  
Dependent Manner ◽  
Cell Crawling

Neutrophil transmigration through venular walls that are composed of endothelial cells (ECs), pericytes, and the venular basement membrane is a key component of innate immunity. Through direct analysis of leukocyte–pericyte interactions in inflamed tissues using confocal intravital microscopy, we show how pericytes facilitate transmigration in vivo. After EC migration, neutrophils crawl along pericyte processes to gaps between adjacent pericytes in an ICAM-1–, Mac-1–, and LFA-1–dependent manner. These gaps were enlarged in inflamed tissues through pericyte shape change and were used as exit points by neutrophils in breaching the venular wall. The findings identify previously unknown roles for pericytes in neutrophil transmigration in vivo and add additional steps to the leukocyte adhesion cascade that supports leukocyte trafficking into sites of inflammation.

Endotoxin Alteration of the Mucopolysaccharide Blood Vessel Coating in Rats

1974 ◽  
Vol 32 ◽  
pp. 148-149
Author(s):  
D. E. Philpott ◽  
A. Takahashi
Keyword(s):  
Skeletal Muscle ◽  
Endothelial Cells ◽  
Salivary Gland ◽  
Carotid Artery ◽  
Basement Membrane ◽  
Coronary Vessels ◽  
Ruthenium Red ◽  
E Coli ◽  
Old Rats ◽  
The Brain

Two month, eight month and two year old rats were treated with 10 or 20 mg/kg of E. Coli endotoxin I. P. The eight month old rats proved most resistant to the endotoxin. During fixation the aorta, carotid artery, basil arartery of the brain, coronary vessels of the heart, inner surfaces of the heart chambers, heart and skeletal muscle, lung, liver, kidney, spleen, brain, retina, trachae, intestine, salivary gland, adrenal gland and gingiva were treated with ruthenium red or alcian blue to preserve the mucopolysaccharide (MPS) coating. Five, 8 and 24 hrs of endotoxin treatment produced increasingly marked capillary damage, disappearance of the MPS coating, edema, destruction of endothelial cells and damage to the basement membrane in the liver, kidney and lung.

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