Mechanism of rhinovirus-induced changes in airway smooth muscle responsiveness.

Hákonarson, Hákon; Maskeri, Neil; Carter, C; Hodinka, Richard L.; Campbell, Donald E.; Grunstein, Michael

doi:10.1172/jci4141

Cited by 75 publications

(85 citation statements)

References 58 publications

(63 reference statements)

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“…NHBE cell monolayers were washed and incubated with anti-ICAM-1 monoclonal antibodies (mAb) (R1/1.1 Boerhinger Ingelheim) at separate concentrations of 4, 8, and 16 g/ml for 1 h at 37°C under 5% CO 2 -humidified air (24). After which the anti-ICAM-1 mAb solution was removed, and cell monolayers were washed and inoculated with HRV-14 at a concentration of 10 2.5 TCID 50 /ml for 90 min at 34°C under 5% CO 2 -humidified air.…”

Section: Methodsmentioning

confidence: 99%

Human Rhinovirus Selectively Modulates Membranous and Soluble Forms of Its Intercellular Adhesion Molecule–1 (ICAM-1) Receptor to Promote Epithelial Cell Infectivity

Whiteman

Bianco

Knight

et al. 2003

Journal of Biological Chemistry

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Human rhinoviruses are responsible for many upper respiratory tract infections. 90% of rhinoviruses utilize intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, which also plays a critical role in recruitment of immune effector cells. Two forms of this receptor exist; membrane-bound (mICAM-1) and soluble ICAM-1 (sICAM-1). The soluble receptor may be produced independently from the membrane-bound form or it may be the product of proteolytic cleavage of mICAM-1. The ratio of airway epithelial cell expression of mICAM-1 to the sICAM-1 form may influence cell infectivity and outcome of rhinovirus infection. We therefore investigated the effect of rhinovirus on expression of both ICAM-1 receptors in normal human bronchial epithelial cells. We observed separate distinct messenger RNA transcripts coding for mICAM-1 and sICAM-1 in these cells, which were modulated by virus. Rhinovirus induced mICAM-1 expression on epithelial cells while simultaneously down-regulating sICAM-1 release, with consequent increase in target cell infectivity. The role of protein tyrosine kinases was investigated as a potential mechanistic pathway. Rhinovirus infection induced rapid phosphorylation of intracellular tyrosine kinase, which may be critical in up-regulation of mICAM-1. Elucidation of the underlying molecular mechanisms involved in differential modulation of both ICAM-1 receptors may lead to novel therapeutic strategies. Human rhinoviruses (HRV)1 are the most frequent cause of upper respiratory tract infections known as the "common cold." Although these infections are generally mild and self-limiting, they inflict a heavy economical burden due to high loss of productivity and medical costs (1). Currently, there is no effective treatment for HRV infections; over the counter cold remedies only alleviate the symptoms but do not eradicate the virus.Primarily, HRV target epithelial cells for attachment and entry. These cells express intercellular adhesion molecule 1 (ICAM-1), the receptor for 90% of HRV serotypes (2). Both this major group of HRV and the 10% of HRV that use alternative receptors for cell attachment enhance cell surface ICAM-1 expression (3). This glycoprotein, belonging to the immunoglobulin supergene family, consists of five Ig-like domains (4); domains 1 and 2 have been shown to fit snugly in a key-lock relationship into reciprocal canyons on the HRV shell (5). In addition, to this critical role as a docking molecule during HRV infection, ICAM-1 through separate domains with its cognate ligand LFA-1 (CD18/CD11a) drives the migration of immuneeffector cells to sites of inflammation (6). While most studies refer to the membranous form of ICAM-1, a soluble form (sICAM-1) has also been described (7). The molecular mass of sICAM-1 is similar to the molecular mass of the extracellular domain of ICAM-1 (80 -114 kDa) depending on the level of glycosylation, suggesting that this soluble circulating form of ICAM-1 consists of most of the extracellular domain of membranous ICAM-1 (7). Several circulating isoform...

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Section: Methodsmentioning

confidence: 99%

Human Rhinovirus Selectively Modulates Membranous and Soluble Forms of Its Intercellular Adhesion Molecule–1 (ICAM-1) Receptor to Promote Epithelial Cell Infectivity

Whiteman

Bianco

Knight

et al. 2003

Journal of Biological Chemistry

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“…Incubation of rhinovirus with airway smooth muscle cells increases airway smooth muscle responsiveness to acetylcholine and attenuated relaxation to isoprenaline, an effect related to diminished isoprenaline-induced cAMP accumulation and upregulated expression of G i a 3 , effects that were triggered by binding of the rhinovirus to its ICAM-1 receptor in airway smooth muscle [81].…”

Section: Effects Of Inflammatory Factors On Airway Smooth Muscle Contmentioning

confidence: 98%

Airway smooth muscle cells: contributing to and regulating airway mucosal inflammation?

Chung

2000

Eur Respir J

130

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In addition to its contractile properties, airway smooth muscle may contribute to the pathogenesis of asthma by increased proliferation, and by the expression and secretion of pro‐inflammatory cytokines and mediators. Studies of airway smooth muscle cells in culture have shown that many mitogenic mediators can induce proliferation, and that these may therefore, contribute to the increase in airway smooth muscle mass observed in asthma. Other mechanisms for airway smooth muscle proliferation include the interaction with inflammatory cells such as T‐cells and eosinophils. Airway smooth muscle cells may also be a source of inflammatory mediators and cytokines, in particular chemokines, thus implicating airway smooth muscle cells as contributors to the inflammatory mechanisms of asthma. The pro‐activating signals for converting airway smooth muscle cells into a proliferative and secretory cell in asthma are unknown, but may include viruses and immunoglobulin E. Airway smooth muscle contractility may also be altered in response to inflammation. Airway smooth muscle cells may play an important interactive role with inflammatory and other structural cells, contributing to inflammation, injury and repair of the airways. Such a recognition makes it imperative to consider the airway smooth muscle as a target of therapeutic drugs for suppressing not only the contractile but also the proliferative and secretory effects of asthma.

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“…The lower support was secured to the base of the organ bath, and the upper support was attached via a gold chain to a Grass FT.03C force transducer (Validyne Engineering, Northridge, CA) from which isometric tension was continuously displayed on a multichannel recorder, as previously described in our laboratory (21,22). Care was taken to place the membranous portion of the trachea between the supports to maximize the recorded tension generated by the contracting trachealis muscle.…”

Section: Pharmacodynamic Studiesmentioning

confidence: 99%

“…The baths were aerated with 5% CO 2 in oxygen; a pH of 7.35-7.40 was maintained, and the organ bath temperature was held at 37°C. Passive resting tension of each ASM segment was set at 1.5-2.0 g after each tissue had been passively stretched to a tension of 8 g to optimize the resting length of each segment, as previously described (21,22). The tissues were allowed to equilibrate in the organ baths for 45 min, at which time each tissue was primed with a 1-min exposure to 10 Ϫ4 M acetylcholine (ACh).…”

Section: Pharmacodynamic Studiesmentioning

confidence: 99%

“…The cells were grown in a mixture of 5% smooth muscle basal medium (SmBM), which was supplemented with 10% FBS, insulin (5 ng/ml), epidermal growth factor (10 ng/ml; human recombinant), fibroblast growth factor (2 ng/ml; human recombinant), gentamicin (50 ng/ml), and amphotericin-B (50 ng/ml), as previously described in our laboratory (13,22).…”

Section: Preparation and Treatment Of Cultured Asm Cellsmentioning

confidence: 99%

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Bi-Directional Activation Between Human Airway Smooth Muscle Cells and T Lymphocytes: Role in Induction of Altered Airway Responsiveness

Hákonarson

Kim

Whelan

et al. 2001

The Journal of Immunology

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Because both T lymphocyte and airway smooth muscle (ASM) cell activation are events fundamentally implicated in the pathobiology of asthma, this study tested the hypothesis that cooperative intercellular signaling between activated T cells and ASM cells mediates proasthmatic changes in ASM responsiveness. Contrasting the lack of effect of resting human T cells, anti-CD3-activated T cells were found to adhere to the surface of naive human ASM cells, increase ASM CD25 cell surface expression, and induce increased constrictor responsiveness to acetylcholine and impaired relaxation responsiveness to isoproterenol in isolated rabbit ASM tissues. Comparably, exposure of resting T cells to ASM cells prestimulated with IgE immune complexes reciprocally elicited T cell adhesion to ASM cells and up-regulated T cell expression of CD25. Extended studies demonstrated that: 1) ASM cells express mRNAs and proteins for the cell adhesion molecules (CAMs)/costimulatory molecules, CD40, CD40L, CD80, CD86, ICAM-1 (CD54), and LFA-1 (CD11a/CD18); 2) apart from LFA-1, ASM cell surface expression of the latter molecules is up-regulated in the presence of activated T cells; and 3) pretreatment of ASM cells and tissues with mAbs directed either against CD11a or the combination of CD40 and CD86 completely abrogated both the activated T cell-induced changes in expression of the above CAMs/costimulatory molecules in ASM cells and altered ASM tissue responsiveness. Collectively, these observations identify the presence of bi-directional cross-talk between activated T cells and ASM cells that involves coligation of specific CAMs/costimulatory molecules, and this cooperative intercellular signaling mediates the induction of proasthmatic-like changes in ASM responsiveness.

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Mechanism of rhinovirus-induced changes in airway smooth muscle responsiveness.

Cited by 75 publications

References 58 publications

Human Rhinovirus Selectively Modulates Membranous and Soluble Forms of Its Intercellular Adhesion Molecule–1 (ICAM-1) Receptor to Promote Epithelial Cell Infectivity

Human Rhinovirus Selectively Modulates Membranous and Soluble Forms of Its Intercellular Adhesion Molecule–1 (ICAM-1) Receptor to Promote Epithelial Cell Infectivity

Airway smooth muscle cells: contributing to and regulating airway mucosal inflammation?

Bi-Directional Activation Between Human Airway Smooth Muscle Cells and T Lymphocytes: Role in Induction of Altered Airway Responsiveness

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