Extracellular matrix regulates human airway smooth muscle cell migration

Parameswaran, Krishnan; Radford, Katherine; Zuo, Jianmin; Janssen, Luke J.; O'Byrne, Paul M.; Cox, P. Gerard

doi:10.1183/09031936.04.00113103

Cited by 64 publications

(62 citation statements)

References 36 publications

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“…Using standard, well-established coating procedures [11][12][13], both the tissue culture plastic (96-and 24-well plates) and the inert polyacrylamide elastic (gel blocks) substrates were coated with FN, LN, Col I, Col IV or Col V; proteins (100 μg/ml) were diluted in PBS. In addition, as described by Engler and colleagues [17,18], a mixture of acrylamide (5-10%) and bisacrylamide (0.03-0.3%) was used to vary the rigidity of gel blocks (~1-20 kPa) in the physiological range [19].…”

Section: Surface Coating With Ecm Proteinsmentioning

confidence: 99%

“…In that connection, several ECM constituents have been shown to modulate not only synthetic [10], proliferative [11] and migratory [12] functions of the ASM cell in culture, but also biochemical pathways that are implicated in muscle maturation and contraction [11,13]. Findings reported thus far are limited to cellular expression of smooth muscle markers, however, and it remains unknown if the ASM cell in the synthetic, proliferative or migratory state might be less contractile than a similar cell differentiated into fully the contractile state [10][11][12][13][14]. Moreover, how the contractile state of a muscle might be affected by altered deposition and turnover of ECM remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Cell Stiffness, Contractile Stress and the Role of the Extracellular Matrix.

Kim²,

Ahn

et al. 2009

C72. Airway Remodeling: Functional Consequences

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Here we have assessed the effects of extracellular matrix (ECM) composition and rigidity on mechanical properties of the human airway smooth muscle (ASM) cell. Cell stiffness and contractile stress showed appreciable changes from the most relaxed state to the most contracted state: we refer to the maximal range of these changes as the cell contractile scope. The contractile scope was least when the cell was adherent upon collagen V, followed by collagen IV, laminin, and collagen I, and greatest for fibronectin. Regardless of ECM composition, upon adherence to increasingly rigid substrates, the ASM cell positively regulated expression of antioxidant genes in the glutathione pathway and heme oxygenase, and disruption of a redox-sensitive transcription factor, nuclear erythroid 2 p45-related factor (Nrf2), culminated in greater contractile scope. These findings provide biophysical evidence that ECM differentially modulates muscle contractility and, for the first time, demonstrate a link between muscle contractility and Nrf2-directed responses.

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Section: Surface Coating With Ecm Proteinsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cell Stiffness, Contractile Stress and the Role of the Extracellular Matrix.

Kim²,

Ahn

et al. 2009

C72. Airway Remodeling: Functional Consequences

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“…Further investigation of the mechanisms of cell-matrix interactions are required to define the level of selective block of mesenchymal cell migration that may be therapeutically feasible. PARAMESWARAN et al [16] provide evidence of the importance of the b 1 and a 5 , a v integrins in ASM migration, whereas integrins required for circulating fibrocytes to migrate into wounded tissue remain poorly defined. The authors emphasise that monomeric ECM molecules were used in their study as previous work suggests that fibrillar ECM may suppress chemotaxis [25].…”

mentioning

confidence: 99%

“…The study by PARAMESWARAN et al [16] in the current issue of the European Respiratory Journal adds to their earlier work showing that cys-Leukotrienes (cys-LTs) enhanced chemotactic responses to platelet-derived growth factor [17], by demonstrating that collagens III and V, as well as fibronectin, induce ASM migration by a process known as haptotaxis and that these responses are also enhanced by cys-LTs [16]. Several studies have investigated the pathways that underpin ASM chemotactic/chemokinetic responses.…”

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confidence: 99%

Emigration and immigration of mesenchymal cells: a multicultural airway wall

Stewart¹

2004

Eur Respir J

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Chronic inflammatory disease is accompanied by structural changes that appear to relate to disease severity and duration, and are often considered to be poorly reversible, if at all. The processes underpinning the structural changes are varied, complex and not well understood. It is clear that these structural changes contribute to tissue dysfunction.In asthma, remodelling comprises changes in all compartments of the airway wall, with the epithelium potentially orchestrating a persistent cycle of inflammatory injury and repair [1]. The epithelium is thought to influence the underlying mesenchymal cell network through the release of transforming growth factor-b resulting in the activation of myofibroblasts that secrete excessive amounts of collagen and contribute to the burden of pro-inflammatory cytokines. Such changes in the superficial aspect of the airway recapitulate aspects of the pathogenesis of neointima formation, in which damage to the endothelium initiates a repair response that ultimately may compromise vessel function [2].The most significant cellular component of the airway wall remodelling is an increase in the volume of airway smooth muscle (ASM), which is considered to play a dominant role in the consequences of the airway wall thickening for airway reactivity [3]. The mechanisms of the increase in volume of ASM remain ill-defined despite extensive investigation over the last 15 yrs. Hyperplasia of ASM is well evidenced, but there is also evidence for a more limited hypertrophy [4,5]. The hyperplasia has been ascribed to proliferation in situ of ASM in response to growth factors and inflammatory mediators released during exacerbations of chronic asthma. Several investigations of antigen-induced airway inflammation in experimental animals, particularly those in Brown Norway rats, have demonstrated an increase in proliferation of ASM [6] resulting in an increase in the total number of ASM cells [7]. More recent evidence suggests that a decrease in the rate of ASM apoptosis may also contribute to the hyperplasia [8]. However, recent findings suggest the need to re-evaluate in situ proliferation as the major mechanism underlying the ASM hyperplasia. Neither we [9], nor others [10] have been able to detect increased rates of proliferation of ASM cells in biopsies using Ki67, proliferating cell nuclear antigen or cyclin D1 expression. It may be argued that in chronic asthma the rates of proliferation would be too small to detect an increase over the baseline level of cell turnover. Nevertheless, the lack of evidence for in situ proliferation of ASM in human asthmatic airways is consistent with the antiproliferative nature of the laminin and proteoglycan-rich extracellular matrix (ECM) surrounding the ASM cells in muscle bundles [11,12]. An alternative mechanism for the hyperplasia was identified in a biopsy study by GIZYCKI et al.[13], in which an increase in the number of myofibroblasts was detected within 24 h of segmental challenge of the airways. These myofibroblasts were considered to have differe...

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“…Three subclasses of cysLT receptors have been identified, cysLT 1 R [6-10], cysLT 2 R [6-10] and cysLT 3 R [11,12]. Biological activities such as airway hyperresponsiveness [13], cellular adhesion [14][15][16], cell migration [17,18] and mucus secretion [19] are mediated predominantly through cysLT 1 R activation. Whereas cysLT 2 R has been reported to cause vascular permeability [4,20], blockade of cysLT 3 R appears to prevent hypoxic brain injury [12].…”

mentioning

confidence: 99%

Leukotriene D₄activates β₂-integrin adhesion in human polymorphonuclear leukocytes

Meliton

Muñoz²,

Osan³

et al. 2009

Eur Respir J

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We examined the functional role and mechanisms by which activation of cysteinyl leukotriene-1 receptor (cysLT 1 R) regulates b 2 -integrin adhesion to intercellular adhesion molecule (ICAM)-1 in human polymorphonuclear leukocytes (PMNs) in vitro.Human peripheral blood PMNs and eosinophils were isolated separately from the same mildly atopic donors. Surface expression of cysLT 1 R was identified both in PMNs and in eosinophils by immunofluorescence analysis. Total cysLT 1 R protein was substantially greater in eosinophils than in PMNs as determined by Western blot analysis. However, leukotriene D 4 (LTD 4 ) upregulated b 2 -integrin adhesion of PMNs to ICAM-1 with high efficacy in a time-and concentration-dependent manner. Upregulated b 2 -integrin adhesion of PMNs was related temporally and quantitatively to phosphorylation of 85-kDa cytosolic group IVa phospholipase A2 (gIVaPLA2). Augmented LTD 4 -induced adhesion was blocked significantly by montelukast, a cysLT 1 R antagonist. Trifluoromethylketone (a gIVaPLA2 inhibitor) blocked b 2 -integrin adhesion caused by LTD 4 activation, as did anti-CD18 monoclonal antibody directed against b 2 -integrin on the PMN surface.Our data demonstrate that LTD 4 causes phosphorylation of gIVaPLA2 and upregulation of b 2 -integrin adhesion to ICAM-1 or ICAM-1 surrogate through cysLT 1 R activation. Activation of gIVaPLA2 is a critical step through which b 2 -integrin adhesion is upregulated by the cysLT 1 R expressed on the surface membrane of human PMN.KEYWORDS: Adhesion, cysteinyl leukotriene-1 receptor, group IVa phospholipase A2, polymorphonuclear leukocytes C ysteinyl leukotrienes (cysLTs), prostaglandins and thromboxanes are families of pro-inflammatory mediators arising through metabolism of arachidonic acid. CysLTs are implicated in airway hyperresponsiveness in patients with asthma [1,2]. Leukotriene D 4 (LTD 4 ), a cysLT, is generated extracellularly by gamma-glutamyl transpeptidase from secreted LTC 4 , which is synthesised by intracellular conversion from LTA 4 by LTC 4 synthase [2,3]. LTC 4 and LTD 4 have substantial efficacy in causing airway constriction in asthmatic subjects [1,4,5]. Three subclasses of cysLT receptors have been identified, cysLT 1 R [6-10], cysLT 2 R [6-10] and cysLT 3 R [11,12]. Biological activities such as airway hyperresponsiveness [13], cellular adhesion [14][15][16], cell migration [17,18] and mucus secretion [19] are mediated predominantly through cysLT 1 R activation. Whereas cysLT 2 R has been reported to cause vascular permeability [4,20], blockade of cysLT 3 R appears to prevent hypoxic brain injury [12].The 85-kDa cytosolic group IVa phospholipase A2 (gIVaPLA2) is a critical intracellular messenger protein for cellular adhesion and secretion of bioactive lipid mediators in human eosinophils [21,22] and polymorphonuclear leukocytes (PMNs) [16,23]. Activation of gIVaPLA2 causes production of arachidonate metabolites and lysophospholipids [22][23][24][25][26], which are essential for b 2 -integrin adhesion of granulocytes.Th...

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Extracellular matrix regulates human airway smooth muscle cell migration

Cited by 64 publications

References 36 publications

Cell Stiffness, Contractile Stress and the Role of the Extracellular Matrix.

Cell Stiffness, Contractile Stress and the Role of the Extracellular Matrix.

Emigration and immigration of mesenchymal cells: a multicultural airway wall

Leukotriene D₄activates β₂-integrin adhesion in human polymorphonuclear leukocytes

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Extracellular matrix regulates human airway smooth muscle cell migration

Cited by 64 publications

References 36 publications

Cell Stiffness, Contractile Stress and the Role of the Extracellular Matrix.

Cell Stiffness, Contractile Stress and the Role of the Extracellular Matrix.

Emigration and immigration of mesenchymal cells: a multicultural airway wall

Leukotriene D4activates β2-integrin adhesion in human polymorphonuclear leukocytes

Contact Info

Product

Resources

About

Leukotriene D₄activates β₂-integrin adhesion in human polymorphonuclear leukocytes