scholarly journals CD11/CD18-independent neutrophil adherence to laminin is mediated by the integrin VLA-6

Blood ◽  
1992 ◽  
Vol 79 (6) ◽  
pp. 1545-1552 ◽  
Author(s):  
JF Bohnsack
Keyword(s):  
Basement Membrane ◽  
Critical Event ◽  
Vascular Walls ◽  
Subendothelial Matrix ◽  
Neutrophil Adherence ◽  
Human Pmns ◽  
And Migration ◽  
Coated Surfaces ◽  
Reduced Adherence

Abstract Regulated adherence of polymorphonuclear leukocytes (PMNs) to endothelium and subendothelial matrix is a critical event for PMN localization at and migration into inflammatory sites. We previously reported that human PMNs stimulated in vitro adhere to laminin, the major glycoprotein of mammalian basement membrane, by both CD11/CD18 (beta 2 integrin)-dependent and CD11/CD18-independent mechanisms. This CD11/CD18-independent adherence is inhibited by monoclonal antibodies (MoAbs) directed against the beta 1 subunit of integrins (very late antigens [VLA]). The specific PMN VLA receptor responsible for stimulated CD11/CD18-independent PMN adherence to laminin was not elucidated. We show here that this CD11/CD18-independent adherence is mediated by a member of the beta 1 integrins, VLA-6. MoAbs GoH3 and 450– 30, which bind the alpha 6 subunit of VLA-6, significantly reduced adherence of phorbol myristate acetate-stimulated PMNs to laminin- coated surfaces when CD11/CD18-independent adherence was blocked with anti-CD11/CD18 MoAbs. Furthermore, GoH3 completely inhibited stimulated adherence of CD11/CD18-deficient PMNs to laminin. Analysis by flow cytometry showed that human PMNs express VLA-6. The PMN alpha 6 is identical in size and pl to the platelet alpha 6, but the PMN beta 1 exhibits considerable heterogeneity in molecular weight compared with the platelet beta 1. This activation-dependent adherence receptor for laminin may play a role in PMN interaction with basement membrane laminin during PMN movement through vascular walls.

scholarly journals CD11/CD18-independent neutrophil adherence to laminin is mediated by the integrin VLA-6

Blood ◽  
1992 ◽  
Vol 79 (6) ◽  
pp. 1545-1552 ◽  
Author(s):  
JF Bohnsack
Keyword(s):  
Basement Membrane ◽  
Critical Event ◽  
Vascular Walls ◽  
Subendothelial Matrix ◽  
Neutrophil Adherence ◽  
Human Pmns ◽  
And Migration ◽  
Coated Surfaces ◽  
Reduced Adherence

Regulated adherence of polymorphonuclear leukocytes (PMNs) to endothelium and subendothelial matrix is a critical event for PMN localization at and migration into inflammatory sites. We previously reported that human PMNs stimulated in vitro adhere to laminin, the major glycoprotein of mammalian basement membrane, by both CD11/CD18 (beta 2 integrin)-dependent and CD11/CD18-independent mechanisms. This CD11/CD18-independent adherence is inhibited by monoclonal antibodies (MoAbs) directed against the beta 1 subunit of integrins (very late antigens [VLA]). The specific PMN VLA receptor responsible for stimulated CD11/CD18-independent PMN adherence to laminin was not elucidated. We show here that this CD11/CD18-independent adherence is mediated by a member of the beta 1 integrins, VLA-6. MoAbs GoH3 and 450– 30, which bind the alpha 6 subunit of VLA-6, significantly reduced adherence of phorbol myristate acetate-stimulated PMNs to laminin- coated surfaces when CD11/CD18-independent adherence was blocked with anti-CD11/CD18 MoAbs. Furthermore, GoH3 completely inhibited stimulated adherence of CD11/CD18-deficient PMNs to laminin. Analysis by flow cytometry showed that human PMNs express VLA-6. The PMN alpha 6 is identical in size and pl to the platelet alpha 6, but the PMN beta 1 exhibits considerable heterogeneity in molecular weight compared with the platelet beta 1. This activation-dependent adherence receptor for laminin may play a role in PMN interaction with basement membrane laminin during PMN movement through vascular walls.

scholarly journals The endothelial basement membrane acts as a checkpoint for entry of pathogenic T cells into the brain

2020 ◽  
Vol 217 (7) ◽  
Author(s):  
Xueli Zhang ◽  
Ying Wang ◽  
Jian Song ◽  
Hanna Gerwien ◽  
Omar Chuquisana ◽  
...  
Keyword(s):  
T Cells ◽  
Basement Membrane ◽  
Immune Cell ◽  
Cell Phenotype ◽  
T Cell Infiltration ◽  
And Migration ◽  
Endothelial Basement Membrane ◽  
Laminin 411

The endothelial cell basement membrane (BM) is a barrier to migrating leukocytes and a rich source of signaling molecules that can influence extravasating cells. Using mice lacking the major endothelial BM components, laminin 411 or 511, in murine experimental autoimmune encephalomyelitis (EAE), we show here that loss of endothelial laminin 511 results in enhanced disease severity due to increased T cell infiltration and altered polarization and pathogenicity of infiltrating T cells. In vitro adhesion and migration assays reveal higher binding to laminin 511 than laminin 411 but faster migration across laminin 411. In vivo and in vitro analyses suggest that integrin α6β1- and αvβ1-mediated binding to laminin 511–high sites not only holds T cells at such sites but also limits their differentiation to pathogenic Th17 cells. This highlights the importance of the interface between the endothelial monolayer and the underlying BM for modulation of immune cell phenotype.

scholarly journals Epithelial HVEM promotes basement membrane synthesis and intraepithelial T cell survival and migration

2020 ◽  
Author(s):  
Daisuke Takahashi ◽  
Qingyang Wang ◽  
Goo-Young Seo ◽  
Jr-wen Shui ◽  
Zbigniew Mikulski ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Basement Membrane ◽  
Collagen Iv ◽  
Membrane Synthesis ◽  
Basement Membrane Synthesis ◽  
And Migration ◽  
Membrane Components ◽  
T Cell Survival ◽  
Lymphocyte Populations

SummaryIntraepithelial T cells (IET) provide continuous surveillance of the intestinal epithelium, but little was known about how epithelial-derived signals regulate the IET population. We show that epithelial expression of the herpes virus entry mediator (HVEM), a member of the TNF receptor superfamily (TNFRSF), maintained the survival of small intestine IET, especially innate-like TCRαβ+ cells lacking CD4 and CD8β. Patrolling movement of all CD8α+ IET also was impaired in the absence of HVEM. HVEM-deficient epithelial cells exhibited downregulation of synthesis of basement membrane components, including collagen IV. Collagen IV supported IET survival in vitro via interactions with β1 integrins expressed by the IET; absence of β1 integrins decreased some IET subsets. Therefore, these data define a circuit whereby epithelial cells regulate intestine resident T lymphocyte populations through basement membrane synthesis.

scholarly journals Effect of human serum and some of its components on neutrophil adherence and migration across an epithelium.

1986 ◽  
Vol 102 (5) ◽  
pp. 1868-1877 ◽  
Author(s):  
E B Cramer ◽  
L C Milks ◽  
M J Brontoli ◽  
G K Ojakian ◽  
S D Wright ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Human Serum ◽  
Neutrophil Migration ◽  
Autologous Serum ◽  
Heat Inactivation ◽  
Human Neutrophils ◽  
Epithelial Surface ◽  
Neutrophil Adherence ◽  
And Migration

The effect of human serum and some of its components on the process of transepithelial migration of human neutrophils was investigated in an in vitro system. 10% autologous serum caused an increase in neutrophil adherence to and migration across canine kidney epithelial cells. This increase in neutrophil binding also occurred if the epithelium but not the neutrophils had been preincubated with serum. The binding was lost if the serum was either preabsorbed over the kidney epithelium before use or heat inactivated. Indirect immunofluorescence studies indicated that IgG, IgM, and a component of C3 bound to the epithelial surface, whereas IgA, IgE, or C5a were not detectable. The majority of epithelial cells were immunofluorescent, however epithelial cells with varying degrees of reactivity were also apparent and approximately 5% of the epithelial cells did not bind IgG, IgM, and C3. When epithelia were simultaneously tested for the presence of either IgG, IgM, or C3, and bound neutrophils the few epithelial cells which did not bind IgG or IgM also did not bind C3 or neutrophils. Studies with monoclonal antibodies against Fc and C3 receptors indicate that neutrophil adherence to the epithelial surface was mediated predominately by the receptors for C3b and C3bi. In response to a chemotactic gradient, bound neutrophils were able to detach and migrate across the epithelium. A separate heat-stable factor(s) in serum was able to increase neutrophil migration across the epithelial monolayer. This factor acted independently of the factors which caused the increase in neutrophil binding as the increase in neutrophil migration also occurred under conditions (preabsorption over the kidney epithelium or heat inactivation) that prevented the increase in neutrophil binding. The increase in neutrophil migration may be caused by the permeability-increasing properties of this factor as both serum and heat-inactivated serum lowered the transepithelial electrical resistance an average of 38 and 35%, respectively, in 40 min. Upon removal of serum or heat-inactivated serum, the resistance returned 100 and 81%, respectively, in 5 h.

scholarly journals Neutrophil migration across monolayers of cytokine-prestimulated endothelial cells: a role for platelet-activating factor and IL-8.

1992 ◽  
Vol 117 (3) ◽  
pp. 565-572 ◽  
Author(s):  
T W Kuijpers ◽  
B C Hakkert ◽  
M H Hart ◽  
D Roos
Keyword(s):  
Endothelial Cells ◽  
Neutrophil Migration ◽  
Platelet Activating Factor ◽  
Human Neutrophils ◽  
Neutrophil Adherence ◽  
Paf Receptor ◽  
And Migration ◽  
Web 2086 ◽  
Paf Receptor Antagonist

In a previous study we observed that neutrophils respond with a rapid rise in [Ca2+]i during adherence to cytokine-activated endothelial cells (EC), caused by EC membrane-associated platelet-activating factor (PAF). In the present study, we investigated whether this form of PAF was important in neutrophil adherence and migration across monolayers of rIL-1 beta- or rTNF alpha-prestimulated EC. PAF receptor antagonists prevented neutrophil migration across cytokine-pretreated EC by approximately 60% (P less than 0.005) without interfering with the process of adherence. The antagonists WEB 2086 and L-652,731 had no effect on neutrophil migration across resting EC induced by formylmethionyl-leucyl-phenylalanine (FMLP). A murine anti-IL-8 antiserum was found to also partially inhibit the neutrophil transmigration across cytokine-activated EC. When the anti-IL-8 antiserum was used in combination with a PAF receptor antagonist, neutrophil migration across cytokine-pretreated monolayers of EC was completely prevented. During transmigration, LAM-1 and CD44 on the neutrophils were down-modulated; both WEB 2086 and anti-IL-8 antiserum partially prevented this down-modulation caused by cytokine-prestimulated EC. Our results indicate that human neutrophils are activated and guided by EC-associated PAF and EC-derived IL-8 during the in vitro diapedesis in between cytokine-stimulated EC.

Measurement of Cell Adhesion and Migration on Protein-Coated Surfaces

1991 ◽  
Vol 252 ◽  
Author(s):  
Paul A. DiMilla ◽  
Julie A. Stone ◽  
Steven M. Albelda ◽  
Douglas A. Lauffenburger ◽  
John A. Quinn
Keyword(s):  
Cell Adhesion ◽  
Critical Shear Stress ◽  
Cell Movement ◽  
Time Lapse ◽  
Tissue Cell ◽  
Cell Adhesion And Migration ◽  
And Migration ◽  
Coated Surfaces

ABSTRACTThe performance of biomaterials forin vivoandin vitroapplications can depend critically on tissue cell adhesion and migration. We have been investigating the role that specific reversible interactions between cell adhesion receptors and complementary substratum-bound ligands play in the regulation of cell adhesion and migration. With an axisymmetric radial flow detachment assay (RFDA) [1] we measured cell-substratum adhesive strength for human smooth muscle cells (HSMCs) on surfaces coated with type IV collagen (CIV). We found that the critical shear stress for detachment increased linearly with increasing CIV coating concentration. Using time-lapse videomicroscopy and image analysis we tracked the movement of individual HSMCs over similar CIV-coated surfaces. Cell speed and persistence were determined for variations in CIV coating concentration by applying a persistent random walk model for individual cell movement. Cell speed reached a maximum at an intermediate concentration of CIV, supporting the hypothesis that an optimal cell-substratum adhesiveness exists for HSMC movement. This combination of techniques for measuring adhesion and motility provides a valuable tool to examine the role of cell-biomaterial interactions on cell behavior.

Endogenous hydrogen sulfide sulfhydrates IKKβ at cysteine 179 to control pulmonary artery endothelial cell inflammation

2019 ◽  
Vol 133 (20) ◽  
pp. 2045-2059 ◽  
Author(s):  
Da Zhang ◽  
Xiuli Wang ◽  
Siyao Chen ◽  
Selena Chen ◽  
Wen Yu ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Endothelial Cell ◽  
Pulmonary Artery ◽  
Cell Model ◽  
Site Directed Mutagenesis ◽  
Critical Event ◽  
Hypertensive Rats ◽  
Pulmonary Artery Endothelial Cell

Abstract Background: Pulmonary artery endothelial cell (PAEC) inflammation is a critical event in the development of pulmonary arterial hypertension (PAH). However, the pathogenesis of PAEC inflammation remains unclear. Methods: Purified recombinant human inhibitor of κB kinase subunit β (IKKβ) protein, human PAECs and monocrotaline-induced pulmonary hypertensive rats were employed in the study. Site-directed mutagenesis, gene knockdown or overexpression were conducted to manipulate the expression or activity of a target protein. Results: We showed that hydrogen sulfide (H2S) inhibited IKKβ activation in the cell model of human PAEC inflammation induced by monocrotaline pyrrole-stimulation or knockdown of cystathionine γ-lyase (CSE), an H2S generating enzyme. Mechanistically, H2S was proved to inhibit IKKβ activity directly via sulfhydrating IKKβ at cysteinyl residue 179 (C179) in purified recombinant IKKβ protein in vitro, whereas thiol reductant dithiothreitol (DTT) reversed H2S-induced IKKβ inactivation. Furthermore, to demonstrate the significance of IKKβ sulfhydration by H2S in the development of PAEC inflammation, we mutated C179 to serine (C179S) in IKKβ. In purified IKKβ protein, C179S mutation of IKKβ abolished H2S-induced IKKβ sulfhydration and the subsequent IKKβ inactivation. In human PAECs, C179S mutation of IKKβ blocked H2S-inhibited IKKβ activation and PAEC inflammatory response. In pulmonary hypertensive rats, C179S mutation of IKKβ abolished the inhibitory effect of H2S on IKKβ activation and pulmonary vascular inflammation and remodeling. Conclusion: Collectively, our in vivo and in vitro findings demonstrated, for the first time, that endogenous H2S directly inactivated IKKβ via sulfhydrating IKKβ at Cys179 to inhibit nuclear factor-κB (NF-κB) pathway activation and thereby control PAEC inflammation in PAH.

Targeting Matrix Metalloproteinases in Atherosclerosis and Cardiovascular Dysfunction

2019 ◽  
Vol 70 (2) ◽  
pp. 718-720
Author(s):  
Lucia Corina Dima-Cozma ◽  
Sebastian Cozma ◽  
Delia Hinganu ◽  
Cristina Mihaela Ghiciuc ◽  
Florin Mitu
Keyword(s):  
Smooth Muscle ◽  
Matrix Metalloproteinases ◽  
Cholesterol Synthesis ◽  
Balloon Dilation ◽  
Aortic Aneurysms ◽  
Arterial Lesions ◽  
Smooth Muscle Cell Migration ◽  
And Migration

Matrix metalloproteinases (MMPs) are the primary mediators of extracellular remodeling and their properties are useful in diagnostic evaluation and treatment. They are zinc-dependent proteases. MMPs have been involved in the mechanisms of atherosclerosis in various arterial areas, ischemic heart disease and myocardial infarction, atrial fibrillation and aortic aneurysms. Recently, MMP9 has been implicated in dyslipidemia and cholesterol synthesis by the liver. Increased MMP expression and activity has been associated with neointimal arterial lesions and migration of smooth muscle cells after arterial balloon dilation, while MMP inhibition decreases smooth muscle cell migration in vivo and in vitro.

scholarly journals Hypoxic glioma-derived exosomes promote M2-like macrophage polarization by enhancing autophagy induction

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Jianye Xu ◽  
Jian Zhang ◽  
Zongpu Zhang ◽  
Zijie Gao ◽  
Yanhua Qi ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Autophagy Induction ◽  
Antitumor Immunotherapy ◽  
Novel Biomarkers ◽  
And Migration ◽  
Immunosuppressive Microenvironment ◽  
Proliferation And Migration ◽  
Glioma Progression

AbstractExosomes participate in intercellular communication and glioma microenvironment modulation, but the exact mechanisms by which glioma-derived exosomes (GDEs) promote the generation of the immunosuppressive microenvironment are still unclear. Here, we investigated the effects of GDEs on autophagy, the polarization of tumor-associated macrophages (TAMs), and glioma progression. Compared with normoxic glioma-derived exosomes (N-GDEs), hypoxic glioma-derived exosomes (H-GDEs) markedly facilitated autophagy and M2-like macrophage polarization, which subsequently promoted glioma proliferation and migration in vitro and in vivo. Western blot and qRT-PCR analyses indicated that interleukin 6 (IL-6) and miR-155-3p were highly expressed in H-GDEs. Further experiments showed that IL-6 and miR-155-3p induced M2-like macrophage polarization via the IL-6-pSTAT3-miR-155-3p-autophagy-pSTAT3 positive feedback loop, which promotes glioma progression. Our study clarifies a mechanism by which hypoxia and glioma influence autophagy and M2-like macrophage polarization via exosomes, which could advance the formation of the immunosuppressive microenvironment. Our findings suggest that IL-6 and miR-155-3p may be novel biomarkers for diagnosing glioma and that treatments targeting autophagy and the STAT3 pathway may contribute to antitumor immunotherapy.

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