Journal Information
Vol. 15. Issue 3.
Pages 461-472 (May - June 2009)
Share
Share
Download PDF
More article options
Vol. 15. Issue 3.
Pages 461-472 (May - June 2009)
Artigo de Revisão/Review Article
Open Access
A intervenção da célula epitelial na asma
The role of the epithelial cell in asthma
Visits
5668
Anabela Mota Pinto1, Ana Todo-Bom2
1 Professora Associada com Agregação de Fisiopatologia – Faculdade de Medicina da Universidade de Coimbra Directora do Instituto de Patologia Geral
2 Assistente Hospitalar Graduada em Imunoalergologia nos Hospitais da Universidade de Coimbra. Doutoramento em Medicina Interna – Pneumologia pela Faculdade de Medicina da Universidade de Coimbra
This item has received

Under a Creative Commons license
Article information
Resumo

Faz-se uma revisão da intervenção da célula epitelial brônquica na fisiopatologia da asma. O epitélio que reveste as vias respiratórias actua como uma barreira física, separando o meio externo do meio interno pul-monar, controla a permeabilidade intercelular e transcelular, e, deste modo, a acessibilidade dos agressores inalantes às células apresentadoras de antigénio en-volvidas na resposta imunoinflamatória. As células epiteliais unidas por tight junctions contribuem para a integridade das vias aéreas e expressam poliovirus re-ceptor–related protein (PRR), toll like receptors (TLR) e protease-activated receptors (PAR), que reconhecem agentes bacterianos e alergénios. A sua disfunção transforma-as em fonte de mediadores intervenientes na inflamação.

A interacção bidireccional entre, por um lado, o epitélio e os elementos constitutivos do brônquio e por outro, as partículas inaladas, tem subjacente a forma-ção de uma unidade, com identidade própria desig-nada EMTU – epithelial mesenchymal trophic unit. Esta extensa intervenção coloca a célula epitelial no centro de acção da cronicidade e remodelação do pro-cesso asmático.

As doenças infecciosas e o stress ambiental são capazes de induzir alterações a nível da célula epitelial suscep-tíveis de modificar a sua resposta a estimulações futu-ras, nomeadamente a ampliar a resposta a outras agressões infecciosas por acção sinérgica das vias de sinalização.

O epitélio brônquico tem assim funções de barreira que lhe permite exercer uma permeabilidade selectiva, a nível intracelular e transcelular, é ainda metabolica-mente activo pelas capacidade de produzir mediadores quimiotácticos e citocinas envolvidos no recrutamento e na activação celular, com repercussão na broncomo-tricidade e na remodelação da parede brônquica.

Rev Port Pneumol 2009; XV (3): 461-472

Palavras-chave:
Asma
epitélio
inflamação
Abstract

It is done a review of the intervention of the epithelial bronchial cell in the pathophysiology of asthma. The respiratory epithelium acts as a physical barrier that separates the external environment from the pulmonary internal environment. It controls the intercellular and trans-cellular permeability and this way the accessibility of the inhaled pathogens to the antigen presenting cells involved in the immuno-inflammatory response. Epithelial cells connected by tight junctions contribute to the barrier function of the airways. They express a poliovirus receiver – related protein (PRR), toll like receptors (TLRs) and protease-activated receptors (PARs), which recognize bacterial agents and allergens. Its dysfunction turns them into important sources of inflammatory mediators.

The bidirectional interaction between the epithelium and other bronchial wall elements with inhaled particles originates a structure with its own identity, the designated EMTU – Epithelial Mesenchymal Trophic Unit.

These observations support a central role for the epithelial cell in chronic inflammation and in the remodelling of the asthmatic process.

Infectious diseases and environmental stress can acti-vate different cell receptors and signalling pathways that induce changes in the cell surface modifying their response to future stimulations, namely to other infectious aggressions.

The bronchial epithelium has barrier functions with selective permeability; it has metabolic activity producing cytokines and chemokines stimulating the cell’s recruitment and activation, increasing the bronchial reactivity and the remodelling of the airways.

Rev Port Pneumol 2009; XV (3): 461-472

Key-words:
Asthma
epithelium
inflammation
Full text is only aviable in PDF
Bibliografia
[1.]
Bousquet Jean, P.K. Jeffery, W.W. Busse, M. Johnson, A.M. Vignola.
Asthma. From bronchoconstriction to airways inflammation and remodeling.
Am J Respir Crit Care Med, 161 (2000), pp. 1720-1745
[2.]
A. Todo-Bom, A. Mota Pinto.
Fisiopatologia da asma grave.
Rev Port Imunoalergol, 14 (2006), pp. 43-48
[3.]
Hammad Hamida, B.N. Lambrecht, H. Hammad, B.N. Lambrecht.
Recent progress in the biology of airway dendritic cells and implications for understanding the regulation of asthmatic inflammation.
J Allergy Clin Immunol, 118 (2006), pp. 331-336
[4.]
H. Kim Chang.
Regulation of FoxP3+ Regulatory T Cells and Th17 cells by retinoids.
Clin Dev Immunol, 416910 (2008), pp. 1-12
[5.]
Larché Mark.
Regulatory T cells in allergy and asthma.
Chest, 132 (2007), pp. 1007-1014
[6.]
Kearley Jennifer, D.S. Robinson, C.M. Lloyd.
CD4+CD25+ regulatory T cells reverse established allergic airway inflammation and prevent airway remodeling.
J Allergy Clin Immunol, 122 (2008), pp. 617-624
[7.]
Barbato Angelo, G. Turato, S. Baraldo, E. Bazzan, F. Calabrese, C. Panizzolo.
Epithelial damage and angio-genesis in the airways of children with asthma.
Am J Respir Crit Care Med, 174 (2006), pp. 975-981
[8.]
Knight Darryl.
Increased permeability of asthmatic epithelial cells to pollutants: does this mean that they are intrinsically abnormal?.
Clin Exp Allergy, 32 (2002), pp. 1263-1265
[9.]
A.B. Vroling, W.J. Fokkens, C.M. van Drunen.
How epithelial cells detect danger: aiding the immune response.
Allergy, 63 (2008), pp. 1110-1123
[10.]
Colognato Renato, J.R. Slupsky, M. Jendrach, L. Burysek, T. Syrovets, T. Simmet.
Differential expression and regulation of protease-activated receptors in human peripheral monocytes and monocyte-derived antigen-presenting cells.
Blood, 102 (2003), pp. 2645-2652
[11.]
Hammad Hamida, B.N. Lambrecht.
Dendritic cells and epithelial cells: linking innate and adaptive immunity in asthma.
Nature Rev, 8 (2008), pp. 193-204
[12.]
H.Y. Tai, M.F. Tam, H. Chou, H.J. Peng, S.N. Su, D.W. Perng, H.D. Shen.
Pench 13 allergen induces secretion of mediators and degradation of occludin protein of human lung epithelial cells.
[13.]
L. Cortes, A.L. Carvalho, A. Todo-Bom, C. Faro, E. Pires, P. Veríssimo.
Purification of a novel aminopeptidase from the pollen of parietária-judaica that alters epithelial integrity and degrades neuropeptides.
J Allergy Clin Immunol, 118 (2006), pp. 878-884
[14.]
Kawai Taro, S. Akira.
Pathogen recognition with Toll-like receptors.
Curr Opin Immunol, 17 (2005), pp. 338-344
[15.]
J. Laurent Geoffrey.
No Bit PARt for PAR-1.
Am J Respir Cell Mol Biol, 33 (2005), pp. 213-215
[16.]
Suzuki Tomoko, T.J. Moraes, E. Vachon, H.H. Ginzberg, T.T. Huang, M.A. Matthay.
Proteinase-activated receptor-1 mediates elastase-induced apoptosis of human lung epithelial cells.
Am J Respir Cell Mol Biol, 33 (2005), pp. 231-247
[17.]
Ebeling Cory, T. Lam, J.R. Gordon, M.D. Hollenberg, H. Vliagoftis.
Proteinase-activated receptor-2 promotes allergic sensitization to an inhaled antigen through a TNF-mediated pathway.
J Immunol, 179 (2007), pp. 2910-2917
[18.]
Rahman Irfan, S.K. Biswas, A. Kode.
Oxidant and antioxidant balance in the airways and airway diseases.
Eur J Pharmacol, 533 (2006), pp. 222-239
[19.]
A. Comhair Susy, P.R. Bhathena, C. Farver, F.B. Thunnissen, S.C. Erzurum.
Extracellular glutathione peroxidase induction in asthmatic lungs: evidence for redox regulation of expression in human airway epithelial cells.
FASEB J, 15 (2001), pp. 70-78
[20.]
Hammad Hamida, A.S. Charbonnier, C. Duez, G.A. Jacquet Astewart, A.-B. Tonnel, et al.
TH2 polarization by Der p 1– pulsed monocyte-derived dendritic cells is due to the allergic status of the donors.
Blood, 98 (2001), pp. 1135-1141
[21.]
T. Holgate Stephen.
The epithelium takes centre stage in asthma and atopic dermatitis.
Trends Immunol, 28 (2007), pp. 248-251
[22.]
Arima Masafumi, T. Fukuda.
Novel functions of two chemokines in allergic disease thymus and activation-regulated chemokine (TARC)/CCL17 and macrophage-derived chemokine (MDC)/CCL22.
Allergy Clin Immunol Int – J World Allergy Org, 18 (2006), pp. 58-64
[23.]
Ying Sun, B. O’Connor, J. Ratoff, Q. Meng, K. Mallett, D. Cousins, et al.
Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2-attracting chemokines and disease severity.
J Immunol, 174 (2005), pp. 8183-8190
[24.]
Todo-Bom Ana, A. Mota Pinto, S. Vale Pereira, V. Alves, M. Dourado, M. Santos Rosa.
Substance P in long-lasting asthma: Immunoinflammatory pathways.
Allergy Clin Immunol Int – J World Allergy Org, 18 (2006), pp. 242-248
[25.]
Springer Jochen, D.A. Groneberg, R. Pregla, A. Fischer.
Inflammatory cells as source of tachykinin-induced mucus secretion in chronic bronchitis.
Regul Pept, 124 (2005), pp. 195-201
[26.]
T. Holgate Stephen, D.E. Davies, P.M. Lackie, S.J. Wilson, S.M. Puddicombe, J.L. Lordan.
Epithelial-mesenchymal interactions in the pathogenesis of asthma.
J Allergy Clin Immunol, 105 (2000), pp. 193-204
[27.]
Hackett Tillie-Louise, D.A. Knight.
The role of epithelial injury and repair in the origins of asthma.
Curr Opin Allergy Clin Immunol, 7 (2007), pp. 63-68
[28.]
Y. Tesfaigzi.
Processes involved in the repair of in-jured airway epithelia.
Arch Immunol Ther Exp (Warsz), 51 (2003), pp. 283-288
[29.]
Allakhverdi Zoulfia, M.R. Comeau, H.K. Jessup, B.R. Yoon, A. Brewer, S. Chartier, et al.
Thymic stromal lymphopoietin is released by human epithelial cells in response to microbes, trauma, or inflammation and potently activates mast cells.
J Exp Med, 204 (2007), pp. 253-258
[30.]
Liu Yong-Jun, V. Soumelis, N. Watanabe, T. Ito, Y.H. Wang, R.W. Malefyt, et al.
TSLP: an epithelial cell cytokine that regulates T cell differentiation by conditioning dendritic cell maturation.
Annu Rev Immunol, 25 (2007), pp. 193-219
[31.]
J. Leonard Warren.
TSLP: finally in the limelight.
Nature Immunol, 3 (2002), pp. 605-607
[32.]
I.A. Fedorov, S.J. Wilson, D.E. Davies, S.T. Holgate.
Epithelial stress and structural remodelling in childhood asthma.
Thorax, 60 (2005), pp. 389-394
[33.]
Zanini Andrea, A. Chetta, M. Saetta, S. Baraldo, R. D’Ippolito, A. Castagnaro, et al.
Chymase-positive mast cells play a role in the vascular component of airway remodeling in asthma.
J Allergy Clin Immunol, 120 (2007), pp. 329-333
[34.]
Zhang Shaoli, H. Smartt, S.T. Holgate, W.R. Roche.
Growth factors secreted by bronchial epithelial cells control myofibroblast proliferation: an in vitro co-culture model of airway remodeling in asthma.
Lab Invest, 79 (1999), pp. 395-405
[35.]
Phipps Simon, F. Benyahia, T.T. Ou, J. Barkans, D.S. Robinson, A.B. Kay.
Acute allergen-induced airway remodeling in atopic asthma.
Am J Respir Cell Mol Biol, 31 (2004), pp. 626-632
[36.]
C. Willis Brigham, Z. Borok.
TGF-beta-induced EMT: mechanisms and implications for fibrotic lung disease.
Am J Physiol Lung Cell Mol Physiol, 293 (2007), pp. L525-L534
[37.]
Nihlberg Kristian, K. Larsen, A. Hultgardh-Nilsson, A. Malmstrom, L. Bjermer, G. Westergren-Thorsson.
Tissue fibrocytes in patients with mild asthma: a possible link to thickness of reticular basement membrane?.
Respir Res, 7 (2006), pp. 50
[38.]
Chen Yin, Y.H. Zhao, Y.P. Di, R. Wu.
Characterization of human mucin 5B gene expression in airway epithelium and the genomic clone of the amino-terminal and 5-flanking region.
Am J Respir Cell Mol Biol, 25 (2001), pp. 542-553
[39.]
Burgel Pierre-Régis, D. Montani, C. Danel, D.J. Dusser, J.A. Nadel.
A morphometric study of mucins and small airway plugging in cystic fibrosis.
Thorax, 62 (2007), pp. 153-161
[40.]
S. Deshmukh Hitesh, L.M. Case, S.C. Wesselkamper, M.T. Borchers, L.D. Martin, H.G. Shertzer, et al.
Metallo-proteinases mediate mucin 5AC expression by epidermal growth factor receptor activation.
Am J Respir Crit Care Med, 171 (2005), pp. 305-314
[41.]
L. Lordan James, F. Bucchieri, A. Richter, A. Konstantinidis, J.W. Holloway, M. Thornber, et al.
Cooperative effects of Th2 cytokines and allergen on normal and asthmatic bronchial epithelial cells.
J Immunol, 169 (2002), pp. 407-414
[42.]
Zhou Beiyun, D.K. Ann, X. Li, K.J. Kim, H. Lin, P. Minoo, et al.
Hypertonic induction of aquaporin-5: novel role of hypoxia-inducible factor-1.
Am J Physiol Cell Physiol, 292 (2007), pp. C1280-C1290
[43.]
K. Sidhaye Venkataramana, K.S. Schweitzer, M.J. Caterina, L. Shimoda, L.S. King.
Shear stress regulates aquaporin-5 and airway epithelial barrier function.
PNAS, 105 (2008), pp. 3345-3350
[44.]
A. O’Neill Luke, A.G. Bowie.
The family of five: TIR domain-containing adaptors in Toll-like receptor signalling.
Nat Rev Immunol, 7 (2007), pp. 353-364
[45.]
Wright Jo Rae.
The “wisdom” of lung surfactant: balancing host defense and surface tension-reducing functions.
Am J Physiol Lung Cell Mol Physiol, 291 (2006), pp. L847-L850
[46.]
Fleer André, T.G. Krediet.
Innate immunity: toll-like receptors and some more. a brief history, basic organization and relevance for the human newborn.
Neonatology, 92 (2007), pp. 145-157
[47.]
A. McCullers Jonathan, K.C. Bartmess.
Role of neuraminidase in lethal synergism between influenza virus and Streptococcus pneumoniae.
J Infect Dis, 187 (2003), pp. 1000-1009
[48.]
R. Bai Tony, D.A. Knight.
Structural changes in the airways in asthma observations and consequences.
Clin Sci (Lond), 108 (2005), pp. 463-477
[49.]
J. Ratner Adam, E.S. Lysenko, M.N. Paul, J.N. Weiser.
Synergistic proinflammatory responses induced by poly-microbial colonization of epithelial surfaces.
Proc Natl Acad Sci (USA), 102 (2005), pp. 3429-3434
[50.]
J. Goulding, R. Snelgrove, J. Saldana, A. Didierlaurent, M. Cavanagh, E. Gwyer, et al.
Respiratory infections. Do we ever recover?.
Proc Am Thorac Soc, 4 (2007), pp. 618-625
[51.]
J.S. Torday, V.K. Rehan.
The evolutionary continuum from lung development to homeostasis and repair.
Am J Physiol Lung Cell Mol Physiol, 292 (2007), pp. L608-L611
Copyright © 2009. Sociedade Portuguesa de Pneumologia/SPP
Download PDF
Pulmonology
Article options
Tools

Are you a health professional able to prescribe or dispense drugs?