IgE alone promotes human lung mast cell survival through the autocrine production of IL-6Glenn Cruse
Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester and Warwick Medical School, University of Leicester, University Road, Leicester, LE1 9HN, UK
BMC Immunol 9:2. 2008
..In this study we have examined whether IgE alone enhances human lung mast cell (HLMC) survival...
- Chemokine receptor expression in tumour islets and stroma in non-small cell lung cancer
Chandra M Ohri
Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK
BMC Cancer 10:172. 2010
..This study investigated chemokine receptor expression in the tumour islets and stroma in NSCLC...
- Tumour necrosis factor-alpha expression in tumour islets confers a survival advantage in non-small cell lung cancer
Chandra M Ohri
Institute for Lung Health, Glenfield Hospital, Leicester, UK
BMC Cancer 10:323. 2010
..The role of TNFalpha in cancer is complex with both pro-tumourigenic and anti-tumourigenic roles proposed. We hypothesised that anatomical microlocalisation is critical for its function...
Mast cell ion channelsPeter Bradding
Department of Infection, Immunity and Inflammation, University of Leicester Medical School, Glenfield Hospital, Leicester, UK
Chem Immunol Allergy 87:163-78. 2005
..With current techniques it will be possible to identify the molecular origin of these channels and define precisely their role in mast cell function. Mast cell ion channels offer a novel target for the attenuation of allergic disease...
- The role of the mast cell in the pathophysiology of asthma
Peter Bradding
Division of Respiratory Medicine, Institute for Lung Health, University of Leicester Medical School, Leicester, United Kingdom
J Allergy Clin Immunol 117:1277-84. 2006
..The development of potent and specific inhibitors of mast cell secretion, which remain active when administered long-term to asthmatic airways, should offer a novel approach to the treatment of asthma...
- The K+ channels K(Ca)3.1 and K(v)1.3 as novel targets for asthma therapy
Peter Bradding
Department of Infection, Immunity and Inflammation, Institute for Lung Health, University of Leicester, UK
Br J Pharmacol 157:1330-9. 2009
..3 and K(Ca)3.1 in the treatment of asthma...
- Ion channel gene expression in human lung, skin, and cord blood-derived mast cells
Peter Bradding
Division of Respiratory Medicine, Institute for Lung Health, University of Leicester Medical School, United Kingdom
J Leukoc Biol 73:614-20. 2003
....
- The role of the mast cell in asthma: a reassessment
Peter Bradding
Institute for Lung Health, University of Leicester Medical School, UK
Curr Opin Allergy Clin Immunol 3:45-50. 2003
..This review will discuss current advances in this field...
Subclinical phenotypes of asthmaPeter Bradding
Institute for Lung Health and Department of Respiratory Medicine, Glenfield Hospital, UK
Curr Opin Allergy Clin Immunol 10:54-9. 2010
..An accurate and comprehensive clinicopathological classification system therefore remains an important priority for asthma research. The present review discusses the important recent literature in this field...
- Asthma: eosinophil disease, mast cell disease, or both?
Peter Bradding
Department of Infection, Immunity and Inflammation, Institute for Lung Health, University of Leicester, UK
Allergy Asthma Clin Immunol 4:84-90. 2008
..Targeting this mast cell-airway smooth muscle interaction in asthma offers exciting prospects for the treatment of this common disease...
- Induced sputum and bronchial mucosal expression of interleukin-13 is not increased in chronic obstructive pulmonary disease
S Saha
Institute of Lung Health, Leicester, UK
Allergy 63:1239-43. 2008
..We sought to examine IL-13 expression in COPD subjects in induced sputum and bronchus specimens. We hypothesized that inflammatory cells expressing IL-13 localize to the airway smooth muscle bundle and bronchial glands...
- Airway smooth muscle proliferation and survival is not modulated by mast cells
D Kaur
Department of Infection, Inflammation and Immunity, Institute for Lung Health, University of Leicester, Leicester, UK
Clin Exp Allergy 40:279-88. 2010
..The cause of this increased ASM mass is uncertain and whether it is a consequence of ASM-mast cell interactions is unknown...
- Airway smooth muscle chemokine receptor expression and function in asthma
R Saunders
Department of Infection, Immunity and Inflammation, Institute for Lung Health, University of Leicester, Leicester, UK
Clin Exp Allergy 39:1684-92. 2009
..The expression profile of other chemokine receptors by ASM and their function needs to be further explored...
- Sputum eosinophilia in idiopathic pulmonary fibrosis
S S Birring
Institute for Lung Health, Department of Respiratory Medicine, Glenfield Hospital, Leicester, LE3 9QP, United Kingdom
Inflamm Res 54:51-6. 2005
..We tested the hypothesis that the cough and increased cough reflex sensitivity seen in patients with idiopathic pulmonary fibrosis may be due to airway inflammation in a prospective, cross-sectional study...
- Interleukin-4 and -13 expression is co-localized to mast cells within the airway smooth muscle in asthma
C E Brightling
Institute for Lung Health, Leicester Warwick Medical School and University Hospitals of Leicester, Leicester, UK
Clin Exp Allergy 33:1711-6. 2003
..In asthma, Th2 cytokines have been implicated as playing a critical role in the development of airway inflammation and hyper-responsiveness. Whether inflammatory cells within the airway smooth muscle release these cytokines is unknown...
- Resting and activation-dependent ion channels in human mast cells
S M Duffy
Division of Respiratory Medicine, Institute for Lung Health, University of Leicester, Leicester, United Kingdom
J Immunol 167:4261-70. 2001
..Charybdotoxin did not consistently attenuate histamine or leukotriene C(4) release, indicating that the Ca(2+)-activated K(+) current may enhance, but is not essential for, the release of these mediators...
- Voltage-dependent and calcium-activated ion channels in the human mast cell line HMC-1
S M Duffy
Division of Respiratory Medicine, Institute for Lung Health, University of Leicester Medical School, Leicester, United Kingdom
J Leukoc Biol 70:233-40. 2001
..We suggest that this current may contribute to the malignant phenotype while the Ca(2+)-activated K(+) and Cl(-) currents may be involved in cell activation...
- Mast cells express IL-13R alpha 1: IL-13 promotes human lung mast cell proliferation and Fc epsilon RI expression
D Kaur
Department of Infection, Institute for Lung Health, Inflammation and Immunity, University of Leicester, Leicester, UK
Allergy 61:1047-53. 2006
..The IL-13 receptor, IL-13Ralpha1, is expressed on most leukocytes, except T-cells. Evidence to support IL-13Ralpha1 expression on mast cells is limited...
- Induced sputum inflammatory mediator concentrations in eosinophilic bronchitis and asthma
C E Brightling
Glenfield Hospital, Leicester, United Kingdom and Vanderbilt University School of Medicine, Nashville, Tennessee, USA
Am J Respir Crit Care Med 162:878-82. 2000
..64 ng/ml [0.36 to 0.90] and 11-fold [3.3 to 36]), respectively. In conclusion, eosinophilic bronchitis is associated with active airway inflammation with increased release of vasoactive and bronchoconstrictor mediators...
- Activation of human lung mast cells by monomeric immunoglobulin E
G Cruse
Institute for Lung Health, Dept of Infection, Immunity and Inflammation, University of Leicester, UK
Eur Respir J 25:858-63. 2005
..These findings support the hypothesis that immunoglobulin E loading of mast cells within the asthmatic airway contributes to the disordered airway physiology of this disease...
- Mast cell migration to Th2 stimulated airway smooth muscle from asthmatics
A Sutcliffe
Institute for Lung Health, Department of Infection, University of Leicester, Leicester, UK
Thorax 61:657-62. 2006
..Non-asthmatic ASM releases a mediator or mediators that inhibit mast cell migration towards stimulated asthmatic ASM. Specifically targeting mast cell migration into the ASM bundle may provide a novel treatment for asthma...
- The airway smooth muscle CCR3/CCL11 axis is inhibited by mast cells
R Saunders
Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK
Allergy 63:1148-55. 2008
..Mast cells are microlocalized to the airway smooth muscle bundle and whether mast cells influence CCR3-mediated migration is uncertain...
- Functional KCa3.1 K+ channels are required for human lung mast cell migration
G Cruse
Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, Glenfield Hospital, Groby Road, Leicester LE3 9QP, UK
Thorax 61:880-5. 2006
..A study was undertaken to test the hypothesis that blockade of K(Ca)3.1 would attenuate HLMC proliferation and migration...
- Comparison of airway immunopathology of eosinophilic bronchitis and asthma
C E Brightling
Institute for Lung Health, University of Leicester, Division of Respiratory Medicine, Leicester UK
Thorax 58:528-32. 2003
....
- New insights into the role of the mast cell in asthma
C E Brightling
University of Leicester and Warwick Medical School, Leicester, UK
Clin Exp Allergy 33:550-6. 2003
- Attenuation of human lung mast cell degranulation by bronchial epithelium
W Yang
Department of Infection, Immunity, and Inflammation, University of Leicester Medical School, Leicester, UK
Allergy 61:569-75. 2006
..The differential effect with anti-IgE compared with thapsigargin suggests that the mechanism includes interference with the proximal Fc epsilon RI signalling pathway...
- Isolation of filamentous fungi from sputum in asthma is associated with reduced post-bronchodilator FEV1
J Agbetile
Department of Infection, Immunity and Inflammation, Institute for Lung Health, University of Leicester, Leicester, UK
Clin Exp Allergy 42:782-91. 2012
..Fungal sensitization is common in severe asthma, but the clinical relevance of this and the relationship with airway colonization by fungi remain unclear. The range of fungi that may colonize the airways in asthma is unknown...
- New insights into the relationship between airway inflammation and asthma
A J Wardlaw
Department of Respiratory Medicine, Institute for Lung Health, Leicester Warwick Medical School, Glenfield Hospital, Groby Road, Leicester LE3 9QP, U K
Clin Sci (Lond) 103:201-11. 2002
....
- Sputum eosinophilia and the short term response to inhaled mometasone in chronic obstructive pulmonary disease
C E Brightling
Institute for Lung Health, Clinical Sciences Wing, University Hospitals of Leicester, Groby Road, Leicester LE3 9QP, UK
Thorax 60:193-8. 2005
..Whether the response to inhaled corticosteroids is related to the presence of eosinophilic inflammation is unclear...
- Chemokines and their receptors as potential targets for the treatment of asthma
C Palmqvist
Department of Respiratory Medicine, Glenfield Hospital, Leicester, UK
Br J Pharmacol 151:725-36. 2007
..Specific blockade of the responses elicited by chemokines and chemokine receptors responsible for the pathological migration of airway cells could therefore be of great therapeutic interest for the treatment of asthma...
- Human mast cell ion channels
P Bradding
Division of Respiratory Medicine, Institute for Lung Health, University of Leicester Medical School, Glenfield Hospital, Leicester, UK. pbradding @hotmail.com
Clin Exp Allergy 32:979-83. 2002
- The role of mast cells in the structural alterations of the airways as a potential mechanism in the pathogenesis of severe asthma
R J F Carter
Department of Infection, Immunity and Inflammation, Institute for Lung Health, University of Leicester, Clinical Sciences, Glenfield Hospital, UK
Curr Pharm Des 17:685-98. 2011
..Novel targeting of mast cells and their mediators therefore should offer significant therapeutic potential in the treatment of asthma...
- Co-cultivation of mast cells and Fc epsilon RI alpha+ dendritic-like cells from human hip bone marrow
D Kaur
Department of Infection, Immunity and Inflammation, Institute for Lung Health, University of Leicester and Warwick Medical School, University Hospitals of Leicester, Glenfield General Hospital, Leicester, UK
Clin Exp Allergy 35:226-33. 2005
..Hip bone marrow could provide a more convenient less invasive source of mast cell progenitors...
- Sputum and bronchial submucosal IL-13 expression in asthma and eosinophilic bronchitis
Mike A Berry
Institute for Lung Health, University Hospitals of Leicester, Groby Road, Leicester LE3 9QP, UK
J Allergy Clin Immunol 114:1106-9. 2004
..02). CONCLUSION: The increased expression of IL-13 in asthma compared with eosinophilic bronchitis supports the concept that IL-13 may play a critical role in the pathophysiology of asthma...
- Airway hyperresponsiveness is dissociated from airway wall structural remodeling
Salman Siddiqui
Institute of Lung Health, Leicester, United Kingdom
J Allergy Clin Immunol 122:335-41, 341.e1-3. 2008
..However, it is not known whether other features of structural remodeling including increased airway smooth muscle (ASM) mass, matrix deposition, and glandular hyperplasia are also present in EB...
- Human airway smooth muscle promotes human lung mast cell survival, proliferation, and constitutive activation: cooperative roles for CADM1, stem cell factor, and IL-6
Fay Hollins
Department of Infection, Immunity and Inflammation, Institute for Lung Health, University of Leicester Medical School, United Kingdom
J Immunol 181:2772-80. 2008
..Targeting these interactions in asthma might offer a new strategy for the treatment of this common disease...
- Inhibition of human mast cell proliferation and survival by tamoxifen in association with ion channel modulation
S Mark Duffy
Division of Respiratory Medicine, Institute for Lung Health, University of Leicester Medical School, Leicester, United Kingdom
J Allergy Clin Immunol 112:965-72. 2003
..This suggests that tamoxifen might be useful in the treatment of mast-cell-mediated diseases, including mastocytosis, asthma, and pulmonary fibrosis...
- Functional transient receptor potential melastatin 7 channels are critical for human mast cell survival
Rob C E Wykes
Department of Infection, Immunity and Inflammation, Institute for Lung Health, University of Leicester, Leicester, United Kingdom
J Immunol 179:4045-52. 2007
..In summary, HLMC and human mast cell lines express the nonselective cation channel TRPM7 whose presence is essential for cell survival...
- The K+ channel iKCA1 potentiates Ca2+ influx and degranulation in human lung mast cells
S Mark Duffy
Department of Infection, Immunity and Inflammation, Institute for Lung Health, University of Leicester Medical School, UK
J Allergy Clin Immunol 114:66-72. 2004
..CONCLUSION: Opening of iKCA1 enhances IgE-dependent Ca2+ influx and histamine release in HLMCs. Inhibition of iKCA1 may provide a novel approach to the treatment of mast cell-mediated disease...
- Adenosine closes the K+ channel KCa3.1 in human lung mast cells and inhibits their migration via the adenosine A2A receptor
S Mark Duffy
Department of Infection, Immunity and Inflammation, Institute for Lung Health, University of Leicester, and Glenfield Hospital, Leicester, UK
Eur J Immunol 37:1653-62. 2007
..1, providing a clearly defined mechanism by which adenosine inhibits HLMC migration and degranulation. A2A receptor agonists with channel-modulating function may be useful for the treatment of mast cell-mediated disease...
- Increased sputum and bronchial biopsy IL-13 expression in severe asthma
Shironjit K Saha
Institute for Lung Health, Clinical Sciences Wing, University Hospitals of Leicester, Leicester, United Kingdom
J Allergy Clin Immunol 121:685-91. 2008
..The importance of IL-13 in the asthma paradigm is supported by increased expression in human subjects, particularly in patients with mild-to-moderate asthma. However, the role of IL-13 in severe asthma needs to be further defined...
- Pathological features and inhaled corticosteroid response of eosinophilic and non-eosinophilic asthma
Mike Berry
Institute for Lung Health, Glenfield Hospital, Leicester LE3 9QP, UK
Thorax 62:1043-9. 2007
..However, little is known about the underlying airway immunopathology and there are no data from placebo-controlled studies examining the effect of inhaled corticosteroids...
- Human lung mast cells adhere to human airway smooth muscle, in part, via tumor suppressor in lung cancer-1
Weidong Yang
Department of Infection, Immunity and Inflammation, Institute for Lung Health, University of Leicester Medical School, Leicester, United Kingdom
J Immunol 176:1238-43. 2006
..This supports the hypothesis that adhesion is important in the recruitment and retention of HLMC by the ASM in asthma, and for the functional interaction of these cells...
- Mast-cell infiltration of airway smooth muscle in asthma
Christopher E Brightling
Division of Respiratory Medicine, Institute for Lung Health, Leicester-Warwick Medical School and University Hospitals of Leicester, Leicester, United Kingdom
N Engl J Med 346:1699-705. 2002
..T cells and eosinophils were not usually seen in the airway smooth muscle in any of the groups. CONCLUSIONS: The infiltration of airway smooth muscle by mast cells is associated with the disordered airway function found in asthma...
- The CXCL10/CXCR3 axis mediates human lung mast cell migration to asthmatic airway smooth muscle
Christopher E Brightling
Institute for Lung Health, Department of Infection, Inflammation and Immunity, Leicester Warwick Medical School and University Hospitals of Leicester, Leicester, United Kingdom
Am J Respir Crit Care Med 171:1103-8. 2005
..These results suggest that inhibition of the CXCL10/CXCR3 axis offers a novel target for the treatment of asthma...
- Beta2-adrenoceptor regulation of the K+ channel iKCa1 in human mast cells
S Mark Duffy
Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK
FASEB J 19:1006-8. 2005
..Furthermore, the degree of constitutive beta2-receptor "tone" may control the threshold for human mast cell activation through the regulation of iKCa1...
- The re-emergence of the mast cell as a pivotal cell in asthma pathogenesis
Christopher E Brightling
Institute for Lung Health, Department of Respiratory Medicine, University of Leicester and Warwick Medical School, University Hospitals of Leicester, Groby Road, Leicester, LE3 9QP, UK
Curr Allergy Asthma Rep 5:130-5. 2005
..This suggests that interactions between mast cells and airway smooth muscle cells are critical for the development of the disordered airway physiology in asthma...
- Airway smooth muscle and mast cell-derived CC chemokine ligand 19 mediate airway smooth muscle migration in asthma
Davinder Kaur
Institute for Lung Health, and Department of Infection, Inflammation and Immunity, University of Leicester, Leicester, United Kingdom
Am J Respir Crit Care Med 174:1179-88. 2006
..We hypothesized that this results from migration of ASM or progenitors in response to chemokines derived from ASM or mast cells within the ASM bundle...
- Mast cell infiltration of airway smooth muscle in asthma
Peter Bradding
Respir Med 101:1045; author reply 1046-7. 2007
- Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial
Ruth H Green
Institute for Lung Health, Department of Respiratory Medicine and Thoracic Surgery, Glenfield Hospital, LE3 9PQ, Leicester, UK
Lancet 360:1715-21. 2002
..INTERPRETATION: A treatment strategy directed at normalisation of the induced sputum eosinophil count reduces asthma exacerbations and admissions without the need for additional anti-inflammatory treatment...
- Clinical, radiologic, and induced sputum features of chronic obstructive pulmonary disease in nonsmokers: a descriptive study
Surinder S Birring
Department of Respiratory Medicine, Radiology, and Respiratory Physiology, and Leicester Children s Asthma Centre, Institute for Lung Health, Glenfield Hospital, Leicester, United Kingdom
Am J Respir Crit Care Med 166:1078-83. 2002
..Further investigation of this group may disclose novel mechanisms of fixed airflow obstruction...
- Induced sputum inflammatory mediator concentrations in chronic cough
Surinder S Birring
Department of Respiratory Medicine, Institute for Lung Health, Glenfield Hospital, Leicester, United Kingdom
Am J Respir Crit Care Med 169:15-9. 2004
..Our findings support the view that there is release of inflammatory and tussive mediators in patients with chronic cough and suggest that there might be similarities in the mechanism of cough in a diverse range of conditions...
- Engagement of the EP2 prostanoid receptor closes the K+ channel KCa3.1 in human lung mast cells and attenuates their migration
S Mark Duffy
The Department of Infection, Immunity and Inflammation, Institute for Lung Health, University of Leicester, UK
Eur J Immunol 38:2548-56. 2008
..1 in HLMC and attenuates both chemokine- and PGE(2)-dependent HLMC migration. EP(2) receptor agonists with K(Ca)3.1 modulating function may be useful for the treatment of mast cell-mediated disease...
- TH2 cytokine expression in bronchoalveolar lavage fluid T lymphocytes and bronchial submucosa is a feature of asthma and eosinophilic bronchitis
Christopher E Brightling
Division of Respiratory Medicine, Institute for Lung Health, Leicester-Warwick Medical School and University Hospitals of Leicester, Leicester, United Kingdom
J Allergy Clin Immunol 110:899-905. 2002
....
- Differential expression of CCR3 and CXCR3 by human lung and bone marrow-derived mast cells: implications for tissue mast cell migration
Christopher E Brightling
Institute for Lung Health, Department of Infection, Immunity and Inflammation, Leicester Warwick Medical School and University Hospitals of Leicester, Groby Road, Leicester, LE3 9QP, UK
J Leukoc Biol 77:759-66. 2005
..As CXCR3 ligands are elevated in many pulmonary diseases, CXCR3 may be important for determining the anatomical microlocalization of mast cells within the human lung...
- Vascular remodeling is a feature of asthma and nonasthmatic eosinophilic bronchitis
Salman Siddiqui
Institute of Lung Health, University of Leicester, Leicester, United Kingdom
J Allergy Clin Immunol 120:813-9. 2007
..Increased vascularity and expression of vascular endothelial growth factor (VEGF) are recognized features of the asthmatic airway. The association of vascular remodeling with airway hyperresponsiveness (AHR) is unclear...
- KCa3.1 Ca2+ activated K+ channels regulate human airway smooth muscle proliferation
Malcolm C Shepherd
Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, United Kingdom
Am J Respir Cell Mol Biol 37:525-31. 2007
..1 channels in HASM cells. In addition, we have shown that K(Ca)3.1 channels are important in HASM cell proliferation, making these channels a potential therapeutic target in airway remodeling...
- The reclassification of asthma based on subphenotypes
Ruth H Green
Department of Respiratory Medicine, Glenfield Hospital, Groby Road, Leicester, UK
Curr Opin Allergy Clin Immunol 7:43-50. 2007
..The present review discusses the important literature in this field, placing current work in its historical context...
- Chemokine concentrations and mast cell chemotactic activity in BAL fluid in patients with eosinophilic bronchitis and asthma, and in normal control subjects
Lucy Woodman
Insitute for Lung Health, University of Leicester, Glenfield Hospital, UK
Chest 130:371-8. 2006
..007). CONCLUSION: In subjects with eosinophilic bronchitis, CXCL8 and CXCL10 concentrations were elevated in airway secretions. These chemokines may play a key role in mast cell recruitment to the superficial airway in this condition...
- Evidence of a role of tumor necrosis factor alpha in refractory asthma
Mike A Berry
Institute for Lung Health, University Hospital of Leicester National Health Service Trust, Glenfield Hospital, Leicester, United Kingdom
N Engl J Med 354:697-708. 2006
..08 to 0.55; P=0.01). CONCLUSIONS: Patients with refractory asthma have evidence of up-regulation of the TNF-alpha axis. (ClinicalTrials.gov number, NCT00276029.)...
- Macrophage and mast-cell invasion of tumor cell islets confers a marked survival advantage in non-small-cell lung cancer
Tomas J Welsh
Department of Infection, Immunity, and Inflammation, University of Leicester Medical School, Glenfield Hospital, Leicester, LE3 9QP, United Kingdom
J Clin Oncol 23:8959-67. 2005
..The biologic explanation for this and its implications for the use of adjunctive treatment requires further study...
- C3a, mast cells, and asthma
Peter Bradding
FASEB J 19:1585. 2005
