T lymphocytes adhere to airway smooth muscle cells via integrins and CD44 and induce smooth muscle cell DNA synthesis

Asthma is a disease of airway inflammation and hyperreactivity that is associated with a lymphocytic infiltrate in the bronchial submucosa. The interactions between infiltrating T lymphocytes with cellular and extracellular matrix components of the airway and the consequences of these interactions have not been defined. We demonstrate the constitutive expression of CD44 on human airway smooth muscle (ASM) cells in culture as well as in human bronchial tissue transplanted into severe combined immunodeficient mice. In contrast, basal levels of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expression are minimal but are induced on ASM by inflammatory mediators such as tumor necrosis factor alpha (TNF-alpha). Activated, but not resting T cells, adhere to cultured ASM; stimulation of the ASM with TNF-alpha enhanced this adhesion. Adhesion was partially blocked by monoclonal antibodies (mAb) specific for lymphocyte function-associated antigen 1 (LFA-1) and very late antigen 4 (VLA-4) on T cells and ICAM-1 and VCAM-1 on ASM cells. The observed integrin-independent adhesion was mediated by CD44/hyaluronate interactions as it was inhibited by anti-CD44 mAb 5F12 and by hyaluronidase. Furthermore, the adhesion of activated T lymphocytes induced DNA synthesis in growth-arrested ASM cells. Thus, the interaction between T cells and ASM may provide insight into the mechanisms that induce bronchial inflammation and possibly ASM cell hyperplasia seen in asthma.

• Publication year

  1994

• Venue

  Journal of Experimental Medicine

• Publication date

  1994-09-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1084/JEM.180.3.807PMID 7520473PMCID 2191657
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Guidebook to the extracellular matrix and adhesion proteins

  1995cited by this paper
• Deletions in the cytoplasmic domain of platelet-endothelial cell adhesion molecule-1 (PECAM-1, CD31) result in changes in ligand binding properties

  1994cited by this paper
• Expression of endothelial cell adhesion molecules in human bronchial xenografts.

  1994cited by this paper
• Tumor necrosis factor-alpha stimulates ICAM-1 expression in human vascular smooth muscle cells.

  1993cited by this paper
• CD44 antibody stimulates adhesion of peripheral blood T cells to keratinocytes through the leukocyte function-associated antigen-1/intercellular adhesion molecule-1 pathway.

  1993cited by this paper
• Inducible expression of vascular cell adhesion molecule-1 by vascular smooth muscle cells in vitro and within rabbit atheroma.

  1993cited by this paper
• Regulation of human CD44H and CD44E isoform binding to hyaluronan by phorbol myristate acetate and anti-CD44 monoclonal and polyclonal antibodies.

  1993cited by this paper
• Lymphocyte function-associated antigen 1 dominates very late antigen 4 in binding of activated T cells to endothelium

  1993cited by this paper
• CD44 is necessary for optimal contact allergic responses but is not required for normal leukocyte extravasation

  1993cited by this paper
• Intercellular adhesion molecule-1 (ICAM-1) and endothelial leucocyte adhesion molecule-1 (ELAM-1) expression in the bronchial mucosa of normal and asthmatic subjects.

  1992cited by this paper
• Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma.

  1992cited by this paper
• Requirements for hyaluronic acid binding by CD44: a role for the cytoplasmic domain and activation by antibody

  1992cited by this paper
• CD44 can be activated to function as an hyaluronic acid receptor in normal murine T cells

  1992cited by this paper
• Cytokines in symptomatic asthma airways.

  1992cited by this paper
• Adhesion of Activated T Lymphocytes to Vascular Smooth Muscle Cells and Dermal Fibroblasts is Mediated by β1‐ and β2‐Integrins

  1992cited by this paper
• Adhesion of activated T lymphocytes to vascular smooth muscle cells and dermal fibroblasts is mediated by beta 1- and beta 2-integrins.

  1992cited by this paper
• Differential utilization of ICAM-1 and VCAM-1 during the adhesion and transendothelial migration of human T lymphocytes.

  1991cited by this paper
• Inflammation and cell-cell interactions in airway hyperresponsiveness.

  1991cited by this paper
• Dynamic T-cell changes in peripheral blood and bronchoalveolar lavage after antigen bronchoprovocation in asthmatics.

  1991cited by this paper
• Increased secretion of tumor necrosis factor alpha and interleukin-6 by alveolar macrophages consecutive to the development of the late asthmatic reaction.

  1991cited by this paper
• Four molecular pathways of T cell adhesion to endothelial cells: roles of LFA-1, VCAM-1, and ELAM-1 and changes in pathway hierarchy under different activation conditions

  1991cited by this paper
• Identification of a human peripheral lymph node homing receptor: a rapidly down-regulated adhesion molecule.

  1990cited by this paper
• Intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of asthma.

  1990cited by this paper
• Antibodies against the CD44 p80, lymphocyte homing receptor molecule augment human peripheral blood T cell activation.

  1990cited by this paper
• CD44 is the principal cell surface receptor for hyaluronate.

  1990cited by this paper
• Monoclonal antibodies to Pgp-1/CD44 block lympho-hemopoiesis in long- term bone marrow cultures

  1990cited by this paper
• Vascular cell adhesion molecule-1 mediates lymphocyte adherence to cytokine-activated cultured human endothelial cells.

  1990cited by this paper
• On the species specificity of the interaction of LFA-1 with intercellular adhesion molecules.

  1990cited by this paper
• Hyaluronate can function as a cell adhesion molecule and CD44 participates in hyaluronate recognition

  1990cited by this paper
• MHC class II antigen expression in human vascular smooth muscle cells is induced by interferon-gamma and modulated by tumour necrosis factor and lymphotoxin.

  1990cited by this paper
• Histamine stimulates proliferation of airway smooth muscle and induces c-fos expression.

  1990cited by this paper
• Mucosal inflammation in asthma.

  1990cited by this paper
• A human airway smooth muscle cell line that retains physiological responsiveness.

  1989cited by this paper
• Dual role of the CD44 molecule in T cell adhesion and activation.

  1989cited by this paper
• T-cell receptor cross-linking transiently stimulates adhesiveness through LFA-1

  1989cited by this paper
• A human lymphocyte homing receptor, the hermes antigen, is related to cartilage proteoglycan core and link proteins.

  1989cited by this paper
• TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties.

  1989cited by this paper
• Regulation of Major Histocompatibility Gene Expression in Human Vascular Smooth Muscle Cells

  1989cited by this paper
• Induction of intercellular adhesion molecule 1 on primary and continuous cell lines by pro-inflammatory cytokines. Regulation by pharmacologic agents and neutralizing antibodies.

  1988cited by this paper
• Evolutionary conservation of tissue-specific lymphocyte-endothelial cell recognition mechanisms involved in lymphocyte homing

  1988cited by this paper
• Local allergen challenge and bronchoalveolar lavage of allergic asthmatic lungs. Description of the model and local airway inflammation.

  1987cited by this paper
• Lymphocyte recognition of high endothelium: antibodies to distinct epitopes of an 85-95-kD glycoprotein antigen differentially inhibit lymphocyte binding to lymph node, mucosal, or synovial endothelial cells

  1987cited by this paper
• A monoclonal antibody reactive with 5-bromo-2-deoxyuridine that does not require DNA denaturation.

  1985cited by this paper
• A severe combined immunodeficiency mutation in the mouse

  1983cited by this paper
• Three distinct antigens associated with human T-lymphocyte-mediated cytolysis: LFA-1, LFA-2, and LFA-3.

  1982cited by this paper
• A comparison of the quantitative anatomy of the bronchi in normal subjects, in status asthmaticus, in chronic bronchitis, and in emphysema

  1969cited by this paper

• Mechanistic Insights into Granulocyte-Macrophage Colony Stimulating Factor in Combating Fungal Infections: Diverse Fungal Pathogens.

  2025cites this paper
• Through a Translational Lens: How Does Inflammation Contribute to the Pathogenesis of Asthma and Allergy?

  2025cites this paper
• Induction of a memory‐like CD4+ T‐cell phenotype by airway smooth muscle cells

  2024cites this paper
• T cell and airway smooth muscle interaction: a key driver of asthmatic airway inflammation and remodelling.

  2024cites this paper
• CD4+ T cell‐derived IFN‐γ and LIGHT synergistically upregulate chemokine production from airway smooth muscle cells

  2024cites this paper
• Nanocarrier Based Targeting of Vascular Cell Adhesion Molecule-1 for Diagnosis and Treatment of Atherosclerosis: Current Status and Future Perspectives

  2023cites this paper
• Development of a perfusable, hierarchical microvasculature-on-a-chip model

  2023cites this paper
• Occludin Promotes Adhesion of CD8+ T Cells and Melanocytes in Vitiligo via the HIF-1α Signaling Pathway

  2022cites this paper
• Bronchial smooth muscle cell in asthma: where does it fit?

  2022cites this paper
• Crosstalk Between CD4+ T Cells and Airway Smooth Muscle in Pediatric Obesity-related Asthma.

  2022cites this paper
• Mechanisms of Allergy

  2021cites this paper
• Immunomodulatory Nanomedicine for the Treatment of Atherosclerosis

  2021cites this paper
• [Bronchial smooth muscle mitochondria: A new target for asthma therapy?]

  2020cites this paper
• Interferon‐γ amplifies airway smooth muscle‐mediated CD4+ T cell recruitment by promoting the secretion of C–X–C‐motif chemokine receptor 3 ligands

  2020cites this paper
• Smooth-muscle-derived WNT5A augments allergen-induced airway remodelling and Th2 type inflammation

  2020cites this paper
• Nanoparticle-Based Approaches towards the Treatment of Atherosclerosis

  2020cites this paper
• Hyaluronan Synthesis Inhibition Impairs Antigen Presentation and Delays Transplantation Rejection

  2020cites this paper
• Formation and Maintenance of Tissue Resident Memory CD8+ T Cells after Viral Infection

  2019cites this paper
• Knockdown of TFPI-Anchored Endothelial Cells Exacerbates Lipopolysaccharide-Induced Acute Lung Injury Via NF-κB Signaling Pathway

  2019cites this paper
• Oligo-fucoidan improved unbalance the Th1/Th2 and Treg/Th17 ratios in asthmatic patients: An ex vivo study

  2018cites this paper
• Developmental and pathological roles of BMP/follistatin-like 1 in the lung

  2017cites this paper
• CD44 expression trends of mesenchymal stem-derived cell, cancer cell and fibroblast spheroids on chitosan-coated surfaces

  2016cites this paper
• Rutin improves endotoxin‐induced acute lung injury via inhibition of iNOS and VCAM‐1 expression

  2016cites this paper
• airway smooth muscle and epithelial cells in vivo Repeated allergen inhalations induce DNA synthesis in

  2016cites this paper
• Function of Membrane-Associated Proteoglycans in the Regulation of Satellite Cell Growth.

  2016cites this paper
• Advances in Bronchial Thermoplasty.

  2016cites this paper
• Modulating steroid insensitive pathways in airway smooth muscle cells

  2016cites this paper
• Mast cells in asthma – state of the art

  2016cites this paper
• MicroRNA Mediated Chemokine Responses in Human Airway Smooth Muscle Cells

  2016influential citation
• in airway smooth muscle Invited Review: The circle of life: cell cycle regulation

  2015cites this paper
• Nanotubes Connect CD4+ T Cells to Airway Smooth Muscle Cells: Novel Mechanism of T Cell Survival

  2015cites this paper
• Clinical research on asthma through bronchial biopsy: investigación clínica en asma mediante biopsia bronquial

  2015cites this paper
• Effect of intranasal rosiglitazone on airway inflammation and remodeling in a murine model of chronic asthma

  2015cites this paper
• Gasotransmitters in cancer: from pathophysiology to experimental therapy

  2015cites this paper
• Bronchial thermoplasty in asthma: current perspectives

  2015cites this paper
• Microrna Regulation On The Expression Of CD38 And Other Asthma Related Genes In Human Airway Smooth Muscle Cells

  2015influential citation
• Regulation of pulmonary inflammation by mesenchymal cells.

  2014cites this paper
• PPARγ ligand ciglitazone inhibits TNFα-induced ICAM-1 in human airway smooth muscle cells

  2014cites this paper
• Bronchial epithelial injury in the context of alloimmunity promotes lymphocytic bronchiolitis through hyaluronan expression.

  2014cites this paper
• The investigation of intrinsic abnormalities in the airway smooth muscle cells in asthma

  2014cites this paper
• CXCL1 is a negative regulator of mast cell chemotaxis to airway smooth muscle cell products in vitro

  2014cites this paper
• The ROAD to a focused view of airway smooth muscle and inflammatory cells in asthmatic sensitization: a tribute to Newman Stephens

  2014cites this paper
• New insight into the molecular mechanisms of corticosteroid resistance in asthma

  2014cites this paper
• IL-17A mediates a selective gene expression profile in asthmatic human airway smooth muscle cells.

  2014cites this paper
• CD4+ T cells enhance the unloaded shortening velocity of airway smooth muscle by altering the contractile protein expression

  2014influential citation
• T cell-induced airway smooth muscle cell proliferation via the epidermal growth factor receptor.

  2013cites this paper
• The high affinity IgE receptor (FcεRI) expression and function in airway smooth muscle.

  2013cites this paper
• Mechanisms of allergic diseases

  2013cites this paper
• Functional phenotype of airway myocytes from asthmatic airways.

  2013cites this paper
• Implication du PAR-2 dans le remodelage musculaire lisse bronchique de la physiopathologie de l'asthme

  2013cites this paper
• Dexamethasone Pathway That Is Only Partially Sensitive to B-dependent Signaling Κ Involves an Nf- Human Tracheal Smooth Muscle Cells Up-regulation of Icam-1 by Cytokines In

  2013cites this paper
• Anti-Inflammatory Dimethylfumarate: A Potential New Therapy for Asthma?

  2013cites this paper
• Pro-inflammatory and immunomodulatory functions of airway smooth muscle: emerging concepts.

  2013cites this paper
• Airway smooth muscle in the pathophysiology and treatment of asthma.

  2013cites this paper
• Role of JNK and NF-κB pathways in Porphyromonas gingivalis LPS-induced vascular cell adhesion molecule-1 expression in human aortic endothelial cells.

  2013cites this paper
• Eosinophils Induce Airway Smooth Muscle Cell Proliferation

  2013cites this paper
• Hyaluronic acid influence on platelet-induced airway smooth muscle cell proliferation.

  2012cites this paper
• exposureairway remodeling following repeated allergen Treatment with a sphingosine-1-phosphate analog

  2012cites this paper
• Treatment with a sphingosine-1-phosphate analog inhibits airway remodeling following repeated allergen exposure.

  2012cites this paper
• Airway Smooth Muscle: Is There a Phenotype Associated with Asthma?

  2012cites this paper
• Airway smooth muscle in asthma: just a target for bronchodilation?

  2012cites this paper
• Tissue stroma as a regulator of leukocyte recruitment in inflammation

  2012cites this paper
• Role of IgE in modulating the expression and function of smMLCK in human airway smooth muscle cells

  2012cites this paper
• Accumulating Evidence for Increased Velocity of Airway Smooth Muscle Shortening in Asthmatic Airway Hyperresponsiveness

  2012cites this paper
• Point: alterations in airway smooth muscle phenotype do/do not cause airway hyperresponsiveness in asthma.

  2012cites this paper
• The Pivotal Role of Airway Smooth Muscle in Asthma Pathophysiology

  2011influential citation
• Remodeling in asthma.

  2011cites this paper
• Airway smooth muscle and immunomodulation in acute exacerbations of airway disease

  2011cites this paper
• Airway remodeling in asthma: new mechanisms and potential for pharmacological intervention.

  2011cites this paper
• T-bet is induced by interferon-γ to mediate chemokine secretion and migration in human airway smooth muscle cells.

  2011cites this paper
• Insights into asthmatic airway remodelling through murine models

  2011cites this paper
• INVITED REVIEW SERIES: CUTTING EDGE TECHNOLOGIES

  2011cites this paper
• Does airway smooth muscle express an inflammatory phenotype in asthma?

  2011cites this paper
• Effect of Imatinib on Airway Smooth Muscle Thickening in a Murine Model of Chronic Asthma

  2011cites this paper
• Sphingosine kinase and sphingosine 1-phosphate in asthma.

  2011cites this paper
• Interferons modulate mitogen-induced protein synthesis in airway smooth muscle.

  2010cites this paper
• Pathophysiology of bronchial smooth muscle remodelling in asthma

  2010cites this paper
• Phosphorylation of p50 NF-κB at a Single Serine Residue by DNA-dependent Protein Kinase Is Critical for VCAM-1 Expression upon TNF Treatment*

  2010cites this paper
• Roles of CD44 in chemical-induced liver injury.

  2010cites this paper
• Le rôle de la cellule musculaire lisse bronchique humaine dans le remodelage des voies aériennes dans l’asthme

  2010cites this paper
• Overview of asthma; the place of the T cell.

  2010cites this paper
• Asthma during pregnancy alters immune cell profile and airway epithelial chemokine release

  2010cites this paper
• CETP and Inflammation in lipid metabolism and atherosclerosis

  2010cites this paper
• T Cells localize with proliferating smooth muscle alpha-actin+ cell compartments in asthma.

  2010cites this paper
• Platelets and airway remodeling : Mechanisms involved in platelet-induced fibroblast and airway smooth muscle cell proliferation in vitro

  2010cites this paper
• Mast cell adhesion to bronchial smooth muscle in asthma specifically depends on CD51 and CD44 variant 6

  2010cites this paper
• An imbalance in C/EBPs and increased mitochondrial activity in asthmatic airway smooth muscle cells: novel targets in asthma therapy?

  2009cites this paper
• Noncontractile functions of airway smooth muscle cells in asthma.

  2009cites this paper
• Airway Smooth Muscle

  2009cites this paper
• Asthma persistence versus progression: does airway smooth muscle function predict irreversible airflow obstruction?

  2009cites this paper
• CD40 and OX40 ligand are differentially regulated on asthmatic airway smooth muscle

  2009cites this paper
• The role of the extracellular matrix and specific growth factors in the regulation of inflammation and remodelling in asthma.

  2009cites this paper
• Airway Smooth Muscle Dysfunction in Asthma

  2009cites this paper
• Airway smooth muscle as an immunomodulatory cell.

  2009cites this paper
• Expression and function of the inducible costimulator ligand B7-H2 in human airway smooth muscle cells.

  2009cites this paper
• Biology of Airway Smooth Muscle Cells

  2009cites this paper
• Remodeling in asthma.

  2009cites this paper
• Chapter 13 – The Lymphocyte in Asthma and COPD

  2009cites this paper
• Transcriptional regulation of cytokine function in airway smooth muscle cells.

  2009influential citation
• Primary Murine Airway Smooth Muscle Cells Exposed to Poly(I,C) or Tunicamycin Synthesize a Leukocyte-adhesive Hyaluronan Matrix*

  2009cites this paper