The Role of IgE-Receptors in IgE-Dependent Airway Smooth Muscle Cell Remodelling

Roth, Michael; Zhong, Jun; Zumkeller, Celine; S’ng, Chong Teck; Goulet, Stephanie; Tamm, Michael
February 2013
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
Academic Journal
Background: In allergic asthma, IgE increases airway remodelling but the mechanism is incompletely understood. Airway remodelling consists of two independent events increased cell numbers and enhanced extracellular matrix deposition, and the mechanism by which IgE up-regulates cell proliferation and extracellular matrix deposition by human airway smooth muscle cells in asthma is unclear. Objective: Characterise the role of the two IgE receptors and associated signalling cascades in airway smooth muscle cell remodelling. Methods: Primary human airway smooth muscle cells (8 asthmatics, 8 non-asthmatics) were stimulated with human purified antibody-activated IgE. Proliferation was determined by direct cell counts. Total collagen deposition was determined by Sircol; collagen species deposition by ELISA. IgE receptors were silenced by siRNA and mitogen activated protein kinase (MAPK) signalling was blocked by chemical inhibitors. Results: IgE dose-dependently increased extracellular matrix and collagen deposition by airway smooth muscle cells as well as their proliferation. Specifically in cells of asthma patients IgE increased the deposition of collagen-type-I, -III, –VII and fibronectin, but did not affect the deposition of collagens type-IV. IgE stimulated collagen type-I and type-VII deposition through IgE receptor-I and Erk1/2 MAPK. Proliferation and deposition of collagens type-III and fibronectin involved both IgE receptors as well as Erk1/2 and p38 MAPK. Pre-incubation (30 minutes) with Omalizumab prevented all remodelling effects completely. We observed no changes in gelatinase activity or their inhibitors. Conclusion & Clincal Relevance: Our study provides the molecular biological mechanism by which IgE increases airway remodelling in asthma through increased airway smooth muscle cell proliferation and deposition of pro-inflammatory collagens and fibronectin. Blocking IgE action prevents several aspects of airway smooth muscle cell remodelling. Our findings may explain the recently described reduction of airway wall thickness in severe asthma patients treated with humanised anti-IgE antibodies.


Related Articles

  • Alport syndrome and diffuse leiomyomatosis: Deletions in the 5' end of the COL4A5 collagen gene. Antignac, Corinne; Jing Zhou; Sanak, Marek; Cochat, Pierre; Roussel, Bernard; Deschênes, Georges; Gros, Françoise; Knebelmann, Bertrand; Hors-Cayla, Marie-Claude; Tryggvason, Karl; Marie-Claire Gubler // Kidney International;Nov1992, Vol. 42 Issue 5, p1178 

    Alport syndrome (AS) is an hereditary glomerulonephritis that is mainly inherited as a dominant X-linked trait. Structural abnormalities in the type IV collagen α5 chain gene (COL4A5), which maps to Xq22, have recently been detected in several patients with AS. The association of AS with...

  • Leukaemia inhibitory factor increases myoblast replication and survival and affects extracellular matrix production: combined in vivo and in vitro studies in post-natal skeletal muscle. White, Jason D.; Davies, Marilyn; Grounds, Miranda D. // Cell & Tissue Research;Oct2001, Vol. 306 Issue 1, p129 

    Leukaemia inhibitory factor (LIF) has been reported to specifically enhance myoblast proliferation in vitro and increase the number and size of myotubes in regenerating skeletal muscle in vivo. The present study specifically tests the effect of LIF on myoblast replication in vivo. Administration...

  • IgE Regulates the Expression of smMLCK in Human Airway Smooth Muscle Cells. Balhara, Jyoti; Redhu, Naresh Singh; Shan, Lianyu; Gounni, Abdelilah S. // PLoS ONE;Apr2014, Vol. 9 Issue 4, p1 

    Previous studies have shown that enhanced accumulation of contractile proteins such as smooth muscle myosin light chain kinase (smMLCK) plays a major role in human airway smooth muscle cells (HASM) cell hypercontractility and hypertrophy. Furthermore, serum IgE levels play an important role in...

  • An Age-Wise Comparison of Human Airway Smooth Muscle Proliferative Capacity. Fayon, Michael; Andrieux, Annick; Bara, Imane; Rebola, Muriel; Labbé, André; Marthan, Roger; Berger, Patrick // PLoS ONE;Mar2015, Vol. 10 Issue 3, p1 

    We compared the proliferation of neonatal and adult airway smooth muscle cells (ASMC) with no/moderate lung disease, in glucose- (energy production by glycolysis) or glucose-free medium (ATP production from mitochondrial oxidative phosphorylations only), in response to 10% fetal calf serum (FCS)...

  • A deterministic model of growth factor-induced angiogenesis. Sun, Shuyu; Wheeler, Mary F.; Obeyesekere, Mandri; Patrick, Charles W. // Bulletin of Mathematical Biology;Mar2005, Vol. 67 Issue 2, p313 

    Abstract: Understanding the formation and structure of a capillary network is critical for any reparative strategy since the capillary network dictates tissue survival, hemodynamics, and mass transport. Vascular assembly and patterning has largely been studied using a reductionist approach where...

  • Regulation of mesangial cell proliferation. Schöcklmann, Harald O.; Lang, Stefan; Sterzel, R. Bernd // Kidney International;Oct1999, Vol. 56 Issue 4, p1199 

    Regulation of mesangial cell proliferation. Regardless of the source of injury, an imbalance in the control of mesangial cell proliferation appears to play a direct role in the degree of progressive renal injury and glomerulosclerosis. Some of the regulatory mechanisms include specific soluble...

  • Extracellular matrix as a determinant of signaling responses in glomerular epithelial cells. Cybulsky, Andrey V. // Kidney International;Oct1999, Vol. 56 Issue 4, p1242 

    Extracellular matrix as a determinant of signaling responses in glomerular epithelial cells. Glomerular epithelial cell proliferation occurs in renal diseases such as membranous nephropathy and crescentic glomerulonephritis. To understand the growth factors responsible for the proliferative...

  • Three-dimensional matrix suppresses E2F-controlled gene expression in glomerular mesangial cells. Tsuboi, Nobuo; Yoshida, Hiroaki; Kawamura, Tetsuya; Furukawa, Yusuke; Hosoya, Tatsuo; Yamada, Hisashi // Kidney International;Apr2000, Vol. 57 Issue 4, p1581 

    Three-dimensional matrix suppresses E2F-controlled gene expression in glomerular mesangial cells. Background. Extracellular matrix (ECM) regulates mitogenesis of glomerular mesangial cells. Currently, however, the molecular mechanisms that mediate the control of cell growth by ECM are not fully...

  • IgE induces proliferation in human airway smooth muscle cells: role of MAPK and STAT3 pathways. Redhu, Naresh Singh; Shan, Lianyu; Al-Subait, Duaa; Ashdown, Heather L.; Movassagh, Hesam; Lamkhioued, Bouchaib; Gounni, Abdelilah S. // Allergy, Asthma & Clinical Immunology;2013, Vol. 9 Issue 1, p1 

    Airway remodeling is not specifically targeted by current asthma medications, partly owing to the lack of understanding of remodeling mechanisms, altogether posing great challenges in asthma treatment. Increased airway smooth muscle (ASM) mass due to hyperplasia/hypertrophy contributes...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics