Modulation of Leukocyte Behavior by an InflamedExtracellular Matrix

Schor, Hagai; Vaday, Gayle G.; Lider, Ofer

doi:10.1155/2000/51902

Cited by 46 publications

(36 citation statements)

References 63 publications

(77 reference statements)

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“…MMPs, but not MMP-9, have been shown to cleave collagens to create neopeptides with chemoattractive attributes (20,47). To determine whether MMP-9 is capable of cleaving ECM protein in the joint to create chemoattractive peptides, we cleaved collagen types I, II, IV, and V with MMP-9 and tested the cleaved products for their chemoattractive properties for PBMC using a modified Boyden chamber.…”

Section: Burgdorferi-infected Mmp-9mentioning

confidence: 99%

Matrix Metalloproteinase 9 Plays a Key Role in Lyme Arthritis but Not in Dissemination ofBorrelia burgdorferi

Heilpern

Wertheim

et al. 2009

Infect Immun

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Borrelia burgdorferi, the causative agent of Lyme arthritis, does not produce any exported proteases capable of degrading extracellular matrix despite the fact that it is able to disseminate from a skin insertion site to infect multiple organs. Prior studies have shown that B. burgdorferi induces the host protease, matrix metalloproteinase 9 (MMP-9), and suggested that the induction of MMP-9 may allow the organism to disseminate and produce local tissue destruction. We examined the role of MMP-9 in dissemination of B. burgdorferi and pathogenesis of Lyme arthritis. In a MMP-9؊/؊ mouse model, MMP-9 was not required for the dissemination of the spirochete to distant sites. However, MMP-9 ؊/؊ exhibited significantly decreased arthritis compared to wild-type mice. The decrease in arthritis was not due to an inability to control infection since the spirochete numbers in the joints were identical. Levels of inflammatory chemokines and cytokines were also similar in MMP-9 ؊/؊ and wild-type mice. We examined whether decreased inflammation in MMP-9 ؊/؊ mice may be the result of decreased production of neoattractants by MMP-9-dependent cleavage of collagen. MMP-9 cleavage of type I collagen results in increased monocyte chemoattraction. MMP-9 plays an important role in regulating inflammation in Lyme arthritis, potentially through the cleavage of type I collagen.

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Section: Burgdorferi-infected Mmp-9mentioning

confidence: 99%

Matrix Metalloproteinase 9 Plays a Key Role in Lyme Arthritis but Not in Dissemination ofBorrelia burgdorferi

Heilpern

Wertheim

et al. 2009

Infect Immun

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“…2 During their life cycle, these cells often get into contact with the extracellular matrix (ECM), i.e., thick layers of highly diverse interconnected macromolecules. The ECM functions not only as a mechanical cell scaffold but also as a signaling platform 3 which modulates the inflammatory immune response [4][5][6][7] by providing various physical and biochemical clues to immune cells encountering them. For instance, fibrinogen (Fgn), 8 an ECM protein and a ligand for a number of adhesion receptors, often accumulates at inflammation sites and, therefore, helps immune cells to find places of injury.…”

Section: Introductionmentioning

confidence: 99%

Adhesion kinetics of human primary monocytes, dendritic cells, and macrophages: Dynamic cell adhesion measurements with a label-free optical biosensor and their comparison with end-point assays

et al. 2016

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Monocytes, dendritic cells (DCs), and macrophages (MFs) are closely related immune cells that differ in their main functions. These specific functions are, to a considerable degree, determined by the differences in the adhesion behavior of the cells. To study the inherently and essentially dynamic aspects of the adhesion of monocytes, DCs, and MFs, dynamic cell adhesion assays were performed with a high-throughput label-free optical biosensor [Epic BenchTop (BT)] on surfaces coated with either fibrinogen (Fgn) or the biomimetic copolymer PLL-g-PEG-RGD. Cell adhesion profiles typically reached their maximum at ∼60 min after cell seeding, which was followed by a monotonic signal decrease, indicating gradually weakening cell adhesion. According to the biosensor response, cell types could be ordered by increasing adherence as monocytes, MFs, and DCs. Notably, all three cell types induced a larger biosensor signal on Fgn than on PLL-g-PEG-RGD. To interpret this result, the molecular layers were characterized by further exploiting the potentials of the biosensor: by measuring the adsorption signal induced during the surface coating procedure, the authors could estimate the surface density of adsorbed molecules and, thus, the number of binding sites potentially presented for the adhesion receptors. Surfaces coated with PLL-g-PEG-RGD presented less RGD sites, but was less efficient in promoting cell spreading than those coated with Fgn; hence, other binding sites in Fgn played a more decisive role in determining cell adherence. To support the cell adhesion data obtained with the biosensor, cell adherence on Fgn-coated surfaces 30–60 min after cell seeding was measured with three complementary techniques, i.e., with (1) a fluorescence-based classical adherence assay, (2) a shear flow chamber applying hydrodynamic shear stress to wash cells away, and (3) an automated micropipette using vacuum-generated fluid flow to lift cells up. These techniques confirmed the results obtained with the high-temporal-resolution Epic BT, but could only provide end-point data. In contrast, complex, nonmonotonic cell adhesion kinetics measured by the high-throughput optical biosensor is expected to open a window on the hidden background of the immune cell–extracellular matrix interactions.

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“…However, e.g., the complex regulatory function of the ECM on lymphocyte migration and its modulating role during the inflammatory immune response have gained attention only very recently (Korpos et al, 2010;Schor et al, 2000;Sorokin, 2010;Vaday and Lider, 2000).…”

Section: Introductionmentioning

confidence: 99%

In-situ and label-free optical monitoring of the adhesion and spreading of primary monocytes isolated from human blood: Dependence on serum concentration levels

Orgován

Salánki

Sándor

et al. 2014

Biosensors and Bioelectronics

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Adhesion and spreading of primary monocytes isolated from human blood were monitored utilizing optical waveguide lightmode spectroscopy (OWLS); a highly sensitive label-free biosensor technique using evanescent optical waves generated at a biocompatible surface.Appropriate development on a custom built setup enabled the OWLS cuvette to be operated as a 1.5 ml mini-incubator, controlling both temperature and CO 2 levels. The incubator-equipped OWLS is readily applicable for delicate and long-term studies on sensitive primary cells, demonstrated here through monitoring the serum dependence of the adhesion and spreading of human monocytes. Moreover, the custom-built setup enables the simultaneous monitoring of the position and overall width of the OWLS resonant peaks. This unique feature makes it possible to distinguish the refractive index variations induced by the adsorption of secreted material from refractive index changes provoked by cellular spreading. A definite attachment and spreading activity was observed on the substratum (glassy silica-titania), when the serum level of the culturing medium was 0.0-0.01%.Increasing serum concentration resulted in a steep fall in monocyte surface adhesion and spreading. 1.0% serum level practically abolished all spreading activity measured by OWLS, and the number of attached cells was significantly decreased, too. Serum addition to fully spread cells provoked a reduction in the cell-substratum contact area, clearly detectable by the biosensor. Cell spreading was inhibited by pre-coating the sensor surface with considerable amounts of serum proteins. These findings suggest that monocyte spreading is inhibited by the adsorption of serum biomolecules to the substratum, rather than by soluble factors present in the serum. All of these results were obtained completely non-invasively with real time monitoring; demonstrating the capabilities of OWLS to sensitively monitor the adhesion properties of immune cells isolated from human blood. 3The current study is, therefore, a significant step towards the application of label-free optical biosensors in medical diagnostics.

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Modulation of Leukocyte Behavior by an InflamedExtracellular Matrix

Cited by 46 publications

References 63 publications

Matrix Metalloproteinase 9 Plays a Key Role in Lyme Arthritis but Not in Dissemination ofBorrelia burgdorferi

Matrix Metalloproteinase 9 Plays a Key Role in Lyme Arthritis but Not in Dissemination ofBorrelia burgdorferi

Adhesion kinetics of human primary monocytes, dendritic cells, and macrophages: Dynamic cell adhesion measurements with a label-free optical biosensor and their comparison with end-point assays

In-situ and label-free optical monitoring of the adhesion and spreading of primary monocytes isolated from human blood: Dependence on serum concentration levels

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