Review article: Biomedical intelligence
Vol. 140 No. 3334 (2010)
Airway smooth muscle cells respond directly to inhaled environmental factors
- Michael Roth
- Michael Tamm
Summary
A misled or overreacting immune response is assumed to be the major cause of the most prevalent chronic inflammatory lung diseases, asthma and chronic obstructive pulmonary disease (COPD). The contribution of tissue forming cells, especially of airway smooth muscle cells, to the pathologies of both diseases has only recently attracted some attention. New studies in childhood asthma and a rhesus monkey model strongly suggest a central role of the airway smooth muscle cells in lung development, structure, function and response to environmental factors. Airway smooth muscle cells express and respond to activation of IgE receptors. In addition, airway smooth muscle cells recognise and respond to environmental factors, including allergens and dust, via mechanisms that are independent of the immune system such as PAR2 or calreticulin. Interestingly, these changes occur not on the level of gene activity but on the level of protein synthesis. The reason why these temporary changes become chronic in asthma and COPD remains to be studied.
References
- Eder W, Ege MJ, von Mutius E. The asthma epidemic. N Engl J Med. 2006;355:2226–35.
- Fabbri L, Peters SP, Pavord I, Wenzel SE, Lazarus SC, Macnee W, et al. Allergic rhinitis, asthma, airway biology, and chronic obstructive pulmonary disease in AJRCCM in 2004. Am J Respir Crit Care Med. 2005;171:686–98.
- Weibel ER. What makes a good lung? Swiss Med Wkly. 2009;139:375–86.
- Künzli N, Perez L. Evidence based public health – the example of air pollution. Swiss Med Wkly. 2009;139:242–50.
- Holgate ST. Pathogenesis of asthma. Clin Exp Allergy. 2008;38:872–97.
- Greenberger PA. 7. Immunologic lung disease. J Allergy Clin Immunol. 2008;121(2 Suppl):S393–7.
- London SJ. Gene-air pollution interactions in asthma. Proc Am Thorac Soc. 2007;4:217–20.
- Cohn L, Homer RJ, Niu N, Bottomly K. T helper 1 cells and interferon gamma regulate allergic airway inflammation and mucus production. J Exp Med. 1999;190:1309–18.
- Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986;136:2348–57.
- Hamid Q, Azzawi M, Ying S, Moqbel R, Wardlaw AJ, Corrigan CJ, et al. Expression of mRNA for interleukin-5 in mucosal bronchial biopsies from asthma. J Clin Invest. 1991;87:1541–6.
- Robinson DS, Hamid Q, Ying S, Tsicopoulos A, Barkans J, Bentley AM, et al. Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med. 1992;326:298–304.
- Ying S, Durham SR, Corrigan CJ, Hamid Q, Kay AB. Phenotype of cells expressing mRNA for TH2-type (interleukin 4 and interleukin 5) and TH1-type (interleukin 2 and interferon gamma) cytokines in bronchoalveolar lavage and bronchial biopsies from atopic asthmatic and normal control subjects. Am J Respir Cell Mol Biol. 1995;12:477–87.
- Umetsu DT, DeKruyff RH. Th1 and Th2 CD4+ cells in the pathogenesis of allergic diseases. Proc Soc Exp Biol Med. 1997;215:11–20.
- Chapman RW. Canine models of asthma and COPD. Pulm Pharmacol Ther. 2008;21:731–42.
- WHO/NHLBI Workshop Report. Global strategy for asthma management and prevention. Bethesda, MD: National Institute of Health, National Heart, Lung, and Blood Institute; 1995. Publication No. 95–3659.
- Sano T, Nakamura Y, Matsunaga Y, Takahashi T, Azuma M, Okano Y, et al. FK506 and cyclosporin A inhibit granulocyte/macrophage colony-stimulating factor production by mononuclear cells in asthma. Eur Respir J. 1995;8:1473–8.
- Borger P, Kauffman HF, Postma DS, Vellenga E. Interleukin-4 gene expression in activated human T lymphocytes is regulated by the cyclic adenosine monophosphate-dependent signaling pathway. Blood. 1996;87:691–8.
- Sihra BS, Kon OM, Durham SR, Walker S, Barnes NC, Kay AB. Effect of cyclosporin A on the allergen-induced late asthmatic reaction. Thorax. 1997;52:447–52.
- Leckie MJ, ten Brinke A, Khan J, Diamant Z, O’Connor B, Walls C, et al. Effects of an interleukin-5 blocking monoclonal antibody on eosinophilic airway hyper-responsiveness and the late asthmatic response. Lancet. 2000;356:2144–8.
- Plopper CG, Hyde DM. The non-human primate as a model for studying COPD and asthma. Pulm Pharmacol Ther. 2008;21:755–66.
- Jenkins HA, Cool C, Szefler SJ, Covar R, Brugman S, Gelfand EW, et al. Histopathology of severe childhood asthma: a case series. Chest. 2003;124:32–41.
- Miller LA, Gerriets JE, Tyler NK, Abel K, Schelegle ES, Plopper CG, et al. Ozone and allergen exposure during postnatal development alters the frequency and airway distribution of CD25+ cells in infant rhesus monkeys. Toxicol Appl Pharmacol. 2009;236:39–48.
- Huber H, Koesser K. The pathology of bronchial asthma. Arch Intern Med. 1922;30:689–760.
- Johnson PR, Roth M, Tamm M, Hughes M, Ge Q, King G, Burgess JK, Black JL. Airway smooth muscle cell proliferation is increased in asthma. Am J Respir Crit Care Med. 2001;164:474–7.
- Trian T, Benard G, Begueret H, Rossignol R, Girodet PO, Ghosh D, et al. Bronchial smooth muscle remodeling involves calcium-dependent enhanced mitochondrial biogenesis in asthma. J Exp Med. 2007;204:3173–81.
- Roth M, Johnson PR, Borger P, Bihl MP, Rüdiger JJ, King GG, et al. Dysfunctional interaction of C/EBPalpha and the glucocorticoid receptor in asthmatic bronchial smooth-muscle cells. N Engl J Med. 2004;351:560–74.
- Roth M, Black JL. An imbalance in C/EBPs and increased mitochondrial activity in asthmatic airway smooth muscle cells: novel targets in asthma therapy? Br J Pharmacol. 2009;157:334–41.
- Jesudason EC. Airway smooth muscle: an architect of the lung? Thorax. 2009;64:541–5.
- Ichikawa T, Sugiura H, Koarai A, Yanagisawa S, Kanda M, Hayata A, et al. Peroxynitrite augments fibroblast-mediated tissue remodeling via myofibroblast differentiation. Am J Physiol Lung Cell Mol Physiol. 2008;295:L800–8.
- Fernandes DJ, Bonacci JV, Stewart AG. Extracellular matrix, integrins, and mesenchymal cell function in the airways. Curr Drug Targets. 2006;7:567–77.
- Wicks J, Haitchi HM, Holgate ST, Davies DE, Powell RM. Enhanced upregulation of smooth muscle related transcripts by TGF beta2 in asthmatic (myo) fibroblasts. Thorax. 2006;61:313–9.
- Hackett TL, Warner SM, Stefanowicz D, Shaheen F, Pechkovsky DV, Murray LA, et al. Induction of Epithelial-Mesenchymal Transition in Primary Airway Epithelial Cells from Asthmatic Patients by TGF{beta}1. Am J Respir Crit Care Med. 2009;180:122–33.
- Ferdinands JM, Mannino DM. Obstructive lung disease models: what is valid? COPD. 2008;5:382–93.
- Taylor DR. Risk assessment in asthma and COPD: a potential role for biomarkers? Thorax. 2009;64:261–4.
- Barnes PJ. The cytokine network in asthma and chronic obstructive pulmonary disease. J Clin Invest. 2008;118:3546–56.
- Sturton G, Persson C, Barnes PJ. Small airways: an important but neglected target in the treatment of obstructive airway diseases. Trends Pharmacol Sci. 2008;29:340–5.
- Cosio MG, Saetta M, Agusti A. Immunologic aspects of chronic obstructive pulmonary disease. N Engl J Med. 2009;360:2445–54.
- Sarir H, Henricks PA, van Houwelingen AH, Nijkamp FP, Folkerts G. Cells, mediators and Toll-like receptors in COPD. Eur J Pharmacol. 2008;585:346–53.
- Crystal RG, Randell SH, Engelhardt JF, Voynow J, Sunday ME. Airway epithelial cells: current concepts and challenges. Proc Am Thorac Soc. 2008;5:772–7.
- Thorley AJ, Tetley TD. Pulmonary epithelium, cigarette smoke, and chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2007;2:409–28.
- Tliba O, Amrani Y, Panettieri RA Jr. Is airway smooth muscle the “missing link” modulating airway inflammation in asthma? Chest. 2008;133:236–42.
- Tliba O, Panettieri RA Jr. Regulation of inflammation by airway smooth muscle. Curr Allergy Asthma Rep. 2008;8:262–8.
- Luo SF, Wang CC, Chiu CT, Chien CS, Hsiao LD, Lin CH, et al. Lipopolysaccharide enhances bradykinin-induced signal transduction via activation of Ras/Raf/MEK/MAPK in canine tracheal smooth muscle cells. Br J Pharmacol. 2000;130:1799–808.
- Sukkar MB, Xie S, Khorasani NM, Kon OM, Stanbridge R, Issa R, et al. Toll-like receptor 2, 3, and 4 expression and function in human airway smooth muscle. J Allergy Clin Immunol. 2006;118:641–8.
- Morris GE, Whyte MK, Martin GF, Jose PJ, Dower SK, Sabroe I. Agonists of toll-like receptors 2 and 4 activate airway smooth muscle via mononuclear leukocytes. Am J Respir Crit Care Med. 2005;171:814–22.
- Shan X, Hu A, Veler H, Fatma S, Grunstein JS, Chuang S, et al. Regulation of Toll-like receptor 4-induced proasthmatic changes in airway smooth muscle function by opposing actions of ERK1/2 and p38 MAPK signaling. Am J Physiol Lung Cell Mol Physiol. 2006;291:L324–33.
- Oliver BG, Lim S, Wark P, Laza-Stanca V, King N, Black JL, et al. Rhinovirus exposure impairs immune responses to bacterial products in human alveolar macrophages. Thorax. 2008;63:519–25.
- Oliver BG, Johnston SL, Baraket M, Burgess JK, King NJ, Roth M, et al. Increased proinflammatory responses from asthmatic human airway smooth muscle cells in response to rhinovirus infection. Respir Res. 2006;7:71.
- Gencay MM, Tamm M, Glanville A, Perruchoud AP, Roth M. Chlamydia pneumoniae activates epithelial cell proliferation via NF-kappaB and the glucocorticoid receptor. Infect Immun. 2003;71:5814–22.
- Klagas I, Goulet S, Karakiulakis G, Zhong J, Baraket M, Black JL, et al. Decreased hyaluronan in airway smooth muscle cells from patients with asthma and COPD. Eur Respir J. 2009;34:616–28.
- Dekkers BG, Schaafsma D, Nelemans SA, Zaagsma J, Meurs H. Extracellular matrix proteins differentially regulate airway smooth muscle phenotype and function. Am J Physiol Lung Cell Mol Physiol. 2007;292:L1405–13.
- Slats AM, Janssen K, van Schadewijk A, van der Plas DT, Schot R, van den Aardweg JG et al. Expression of smooth muscle and extracellular matrix proteins in relation to airway function in asthma. J Allergy Clin Immunol. 2008;121:1196–202.
- Zhang W, Gunst SJ. Interactions of airway smooth muscle cells with their tissue matrix: implications for contraction. Proc Am Thorac Soc. 2008;5:32–9.
- Johnson PR, Ammit AJ, Carlin SM, Armour CL, Caughey GH, Black JL. Mast cell tryptase potentiates histamine-induced contraction in human sensitized bronchus. Eur Respir J. 1997;10:38–43.
- Haddon DJ, Antignano F, Hughes MR, Blanchet MR, Zbytnuik L, Krystal G, et al. SHIP1 is a repressor of mast cell hyperplasia, cytokine production, and allergic inflammation in vivo. J Immunol. 2009;183:228–36.
- Hamid Q, Tulic M. Immunobiology of asthma. Annu Rev Physiol. 2009;71:489–507.
- Mascia F, Mariani V, Giannetti A, Girolomoni G, Pastore S. House dust mite allergen exerts no direct proinflammatory effects on human keratinocytes. J Allergy Clin Immunol. 2002;109:532–8.
- Thangam EB, Venkatesha RT, Zaidi AK, Jordan-Sciutto KL, Goncharov DA, Krymskaya VP, et al. Airway smooth muscle cells enhance C3a-induced mast cell degranulation following cell-cell contact. FASEB J. 2005;19:798–800.
- Humbles AA, Lu B, Nilsson CA, Lilly C, Israel E, Fujiwara Y, et al. A role for the C3a anaphylatoxin receptor in the effector phase of asthma. Nature. 2000;406:998–1001.
- Plopper CG, Smiley-Jewell SM, Miller LA, Fanucchi MV, Evans MJ, Buckpitt AR et al. Asthma/allergic airways disease: does postnatal exposure to environmental toxicants promote airway pathobiology? Toxicol Pathol. 2007;35:97–110.
- Hakonarson H, Carter C, Kim C, Grunstein MM. Altered expression and action of the low-affinity IgE receptor FcepsilonRII (CD23) in asthmatic airway smooth muscle. J Allergy Clin Immunol. 1999;104:575–84.
- Roth M, Tamm M. Omalizumab blocks IgE induced cytokine synthesis by asthmatic airway smooth muscle cells. Annals Allergy, Asthma, Immunol 2009 in press.
- Gounni AS, Wellemans V, Yang J, Bellesort F, Kassiri K, Gangloff S, et al. Human airway smooth muscle cells express the high affinity receptor for IgE (Fc epsilon RI): a critical role of Fc epsilon RI in human airway smooth muscle cell function. J Immunol. 2005;175:2613–21.
- Black JL, Marthan R, Armour CL, Johnson PR. Sensitization alters contractile responses and calcium influx in human airway smooth muscle. J Allergy Clin Immunol. 1989;84:440–7.
- Watson N, Bodtke K, Coleman RA, Dent G, Morton BE, Rühlmann E, et al. Role of IgE in hyperresponsiveness induced by passive sensitization of human airways. Am J Respir Crit Care Med. 1997;155:839–44.
- Hakonarson H, Grunstein MM. Autologously up-regulated Fc receptor expression and action in airway smooth muscle mediates its altered responsiveness in the atopic asthmatic sensitized state. Proc Natl Acad Sci U S A. 1998;95:5257–62.
- Chambers LS, Black JL, Poronnik P, Johnson PR. Functional effects of protease-activated receptor-2 stimulation on human airway smooth muscle. Am J Physiol Lung Cell Mol Physiol. 2001;281:L1369–78.
- Chambers LS, Black JL, Ge Q, Carlin SM, Au WW, Poniris M, et al. PAR-2 activation, PGE2, and COX-2 in human asthmatic and nonasthmatic airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2003;285:L619–27.
- Freund-Michel V, Frossard N. Inflammatory conditions increase expression of protease-activated receptor-2 by human airway smooth muscle cells in culture. Fundam Clin Pharmacol. 2006;20:351–7.
- Saleh SM, Mann TS, Peters T, Betts RJ, Henry PJ. Influence of dexamethasone on protease-activated receptor 2-mediated responses in the airways. J Pharmacol Exp Ther. 2008;324:622–30.
- Asokananthan N, Graham PT, Stewart DJ, Bakker AJ, Eidne KA, Thompson PJ, et al. House dust mite allergens induce proinflammatory cytokines from respiratory epithelial cells: the cysteine protease allergen, Der p 1, activates protease-activated receptor (PAR)-2 and inactivates PAR-1. J Immunol. 2002;169:4572–8.
- Cho HJ, Choi JY, Yang YM, Hong JH, Kim CH, Gee HY, et al. House dust mite extract activates apical Cl(-) channels through protease-activated receptor 2 in human airway epithelia. J Cell Biochem. 2010;109:1254–63.
- Adam E, Hansen KK, Astudillo Fernandez O, Coulon L, Bex F, Duhant X, et al. The house dust mite allergen Der p 1, unlike Der p3, stimulates the expression of interleukin-8 in human airway epithelial cells via a proteinase-activated receptor-2-independent mechanism. J Biol Chem. 2006;281:6910–23.
- Kauffman HF, Tamm M, Timmerman JA, Borger P. House dust mite major allergens Der p 1 and Der p 5 activate human airway-derived epithelial cells by protease-dependent and protease-independent mechanisms. Clin Mol Allergy. 2006;4:5.
- Heijink IH, van Oosterhout A, Kapus A. EGFR signaling contributes to house dust mite-induced epithelial barrier dysfunction. Eur Respir J. 2010. Epub ahead of print]PMID: 20351035
- Montagnac G, Yu LC, Bevilacqua C, Heyman M, Conrad DH, Perdue MH, et al. Differential role for CD23 splice forms in apical to basolateral transcytosis of IgE/allergen complexes. Traffic. 2005;6:230–42.
- Li H, Nowak-Wegrzyn A, Charlop-Powers Z, Shreffler W, Chehade M, Thomas S, et al. Transcytosis of IgE-antigen complexes by CD23a in human intestinal epithelial cells and its role in food allergy. Gastroenterology. 2006;131:47–58.