Journal Information
Vol. 35. Issue 2.
Pages 71-78 (February 1999)
Share
Share
Download PDF
More article options
Vol. 35. Issue 2.
Pages 71-78 (February 1999)
Full text access
La suberosis: implicación de los mastocitos broncoalveolares en la génesis de la afectación intersticial
Suberosis: involvement of bronchoalveolar mast cells in the etiology of interstitial disease
Visits
3966
L. Delgado1
Corresponding author
jdelgado@mail.telepac.pt

Correspondencia: Serviço de Imunologia. Faculdade de Medicina do Porto. 4200 Porto. Portugal.
, C. Cuesta, J.A. Fleming Torrinha
Servicio de Inmunología. Facultad de Medicina. Hospital de Sao João. Oporto
J.C. Winck*, J.M. Sapage*, J. Moura e Sá*
* Departamento de Neumología. Centro Hospitalario de Vila Nova de Gaia. Portugal
This item has received
Article information

La enfermedad respiratoria de los trabajadores de la industria del corcho –suberosis– puede presentarse clínicamente bajo la forma de neumonitis de hipersensibilidad (NH) o de enfermedad pulmonar obstructiva (EPO), con un cuadro asmatiforme o de bronquitis crónica. Los mastocitos son importantes células inflamatorias del pulmón que están particularmente implicadas en la liberación rápida de mediadores broncoconstrictores y en la producción de citocinas y mediadores que modulan la actividad de los fibroblastos. Se ha descrito un aumento del número de mastocitos en el lavado broncoalveolar (LBA) en las enfermedades pulmonares intersticiales, indicando su participación en la inflamación crónica y la fibrosis pulmonar.

Objetivos

El objetivo fue valorar la participación de los mastocitos en la inflamación pulmonar intersticial en los trabajadores de la industria del corcho analizando su presencia en el LBA por métodos histoquímicos. Con la posibilidad de una implicación de los mastocitos broncoalveolares en la patogénesis de la suberosis, también estudiamos su relación con los distintos cuadros clínicos de la enfermedad, con los parámetros funcionales respiratorios y con la intensidad de la alveolitis.

Pacientes y métodos

Treinta y un trabajadores de la industria del corcho con síntomas respiratorios relacionados con la exposición ocupacional, evaluados por la historia clínica y ocupacional, examen físico, radiografía de tórax, pletismografía corporal/espirometría, difusión de CO (DLCO), gasometría arterial en reposo y broncofibroscopia con LBA. La clasificación de los enfermos –20 con NH y 11 con EPO–se realizó según criterios clínicos, funcionales y del análisis del líquido del LBA. La cuantificación de los mastocitos fue realizada en frotis de citocentrifugado del LBA comparando dos tinciones distintas –May-Grunwald-Giemsa (MGG) y azul de toluidina (AzTol)– y los recuentos de dos observadores.

Principales resultados

Se confirmó una buena correlación entre los dos métodos de tinción (rs=0,86; p<0,0001) y entre los recuentos de dos observadores (MGG [rs=0,86] y AzTol [rs=0,87]; p<0,0001). El número de mastocitos en el LBA estaba significativamente más elevado en pacientes con NH (X±EPM, 13,4±4,5) que en los que tenían EPO (0,9±0,3; p<0,002, test de Mann-Whitney). El subgrupo de 8 pacientes con mayor compromiso funcional respiratorio -capacidad vital (CV) y/o DLCO<80% del valor esperado- presentaba también un número significativamente más elevado de mastocitos en el LBA (19,9±7,7 frente a 3,5±1,7; p=0,002). También encontramos una correlación negativa entre el número de mastocitos en el LBA y los parámetros funcionales respiratorios: capacidad pulmonar total (CPT) (rs=-0,63; p=0,005) y DLCO (rs=-0,54; p=0,008). El número de mastocitos recuperados en el LBA se correlacionó directa y significativamente con la intensidad de la alveolitis, la celularidad total (rs=0,62; p=0,002), el número absoluto de linfocitos (rs=0,56; p=0,006) y las concentraciones de albúmina (rs=0,68; p=0,003).

Conclusiones

Los resultados obtenidos indican que los mastocitos participan en la respuesta celular del intersticio pulmonar a la inhalación de polvos orgánicos del corcho, caracterizando particularmente las formas de NH. Por otro lado, su reclutamiento a la superficie broncoalveolar parece estar relacionado con la intensidad de la linfocitosis y de la inflamación del intersticio pulmonar, así como en el deterioro de la función respiratoria en estos pacientes.

Palabras clave:
Mastocitos
Suberosis
Neumonitis de hipersensibilidad
Lavado broncoalveolar

Suberosis –the lung disease suffered by cork industry workers– may present in the form of either hypersensitivity pneumonitis (HP) or obstructive pulmonary disease (OPD) with asthma-like symptoms or chronic bronchitis. Mast cells play an important role in pulmonary inflammation and are particularly implicated in the rapid release of mediators in bronchoconstriction and the production of cytokines and mediators of fibroblast activity. Increased numbers of mast cells are present in bronchoalveolar lavage (BAL) fluid in interstitial lung diseases, suggesting that these cells also participate in chronic inflammatory processes and in pulmonary fibrosis.

Objectives

To assess the participation of mas cells in in- terstitial pulmonary inflammation in cork industry workers by histochemically analyzing their presence in BAL fluid. Foresseing the possible implication of bronchoalveolar mast cells in the pathogenesis of suberosis, we also studied their relation to various signs and symptoms of the disease, to res- piratory function parameters and to degree of alveolitis.

Patients and methods

Thirty-one cork industry workers with respiratory symptoms related to occupational exposure were enrolled. Occupational and case histories were taken. Physical examiantions were complemented by chest X-rays, plethysmography/spirometry, fiberoptic bronchos- copy with BAL, and determination of carbon monoxide dif- fussing capacity (DLCO) and arterial blood gases at rest. Patient classification (20 with HP and 11 with OPD) was ba- sed on clinical and functional criteria and analysis of BAL fluid. Mast cells in cytospinned samples treated with two different stains [May-Grunwald-Giemsa (MGG) and Tolui- dine Blue (Tol.Bl.)] were counted by two observers and the results were compared.

Main results

Good correlation between the two staining methods was confirmed (rs=0.86, p<0.0001). Correlation between the two observers was also good (MGG rs=0.86, Yol.Bl. rs=0.87, p<0.0001). The number of mast cells in BAL fluid was significantly higher in patients with HP [13.4±4.5 (x±SEM)] than in those with OPD (0.9±0.3; p<0.002, Mann Whitney test). The subgroup of eight patinets with poorer respiratory function (CV and/or DLCO<80% of reference value) also had higher mast cell counts in BAL (19.9±7.7 versus 3.5±1.7; p=0.002). We also saw a negative relation between mast cell counts in BAL fluid and lung function parameters: total lung capacity (rs=-0.68, p=0.005) and DLCO (rs=-0.54, p=0.008). Mast cell recorvery from BAL fluid was positively related to severity of alveolitis in terms of total cell counts (rs=0.62, p=0.002), absolute lymphocyte counts (rs=0.56, p=0.006) and albumin levels (rs=0.68, p=0.003).

Conclusions

Our findings suggest that mast cells participate in interstitial lung cell response to the inhalation of organic cork dust, particularly when HP is the form of presentation. Moreover, mas cell recruitment on the alveolar surface seems to be related to the intersity of lymphocytosis and interstitial pulmonary inflammation and to lung function deterioration in affected patients.

Key words:
Mast cells
Suberosis
Hypersensitivity pneumonítis
Bronchoalveolur lavage
Full text is only aviable in PDF
Bibliografía
[1.]
R. Ávila, T.G. Villar.
Suberosis: respiratory disease in Cork workers.
Lancet, 1 (1968), pp. 620-623
[2.]
R. Ávila, T.G. Villar.
Respiratory disease in cork workers (suberosis).
Thorax, 28 (1973), pp. 409-423
[3.]
O.P. Sharma.
Hypersensitivity pneumonitis.
Dis Month, (1991), pp. 411-471
[4.]
J.N. Fink.
Hypersensitivity pneumonitis.
Inmmunologycally mediated pulmonary diseases., pp. 399-412
[5.]
R. Ávila, J. Lacey.
The role of Penicilliuim frequentans in suberosis (respiratory disease in cork workers).
Clin Allergy, 4 (1974), pp. 109-117
[6.]
G.W. Hunninghake, J.E. Gadek, O. Kawanami, V.J. Ferrans, R.G. Crystal.
Inflammalory and immune processes in the human lung in health and disease: evaluation by bronchoalveolar lavage.
Am J Pathol, 97 (1979), pp. 149-198
[7.]
Springmever SC. The clinical use of bronchoalveolar lavage. Chest 987; 92: 771-772.
[8.]
H.Y. Reynolds.
Bronchoalveolar lavage has extended the usefulness of bronchoscopy.
Eur Respir Rev, 2 (1992), pp. 48-53
[9.]
Workshop Summary, Guidelines,.
Investigative use of bronchoscopy. lavage and hronchial biopsies in asthma and other air-ways diseases.
Eur Respir .1, 5 (1992), pp. 115-121
[10.]
J. Bousquet, P. Chanez, A. Campbell, J.Y. Lacoste, R. Poston, I. Enander, et al.
Inflammatory processes in asthma.
Int Arch Allergv Immunol, 94 (1991), pp. 227-232
[11.]
M. Luisetti, F. Meloni, P. Ballabio, G. Leo.
Role of bronchial and bronchoalveolar lavage in chronic obstructive lung disease.
Monaldi Arch Chest Dis, 48 (1993), pp. 54-57
[12.]
L. Delgado, J.C. Winck, J.M. Sapage, S. Torres, J.I. Ribeiro, J.M. Sá.
Respiratory disease in cork workers: characterization of suberosis alveolitis bv bronchoalveolar lavage [resumen].
Eur Respir .1, 5 (1992), pp. 503-504
[13.]
L. Delgado, J.P. Ramos, J.C. Winck, C. Cuesta, J.A.F. Torrinha.
Cytotoxic lymphocytes in hypersensitivity pneumonitis [resumen].
Clin Exp Allergy, 23 (1993), pp. 25
[14.]
S.I. Wasserman.
Mast cell biologv.
J Allergy Clin Immunol, 86 (1990), pp. 590-597
[15.]
M. Jordana.
Mast cells and fibrosis –who's on first?.
Am J Respir Cell Mol Biol, 8 (1993), pp. 7-8
[16.]
J.E. Salvaggio, B. Millhollon.
Induction and modulation of pulmonary inflammation by organic dusts: cvtokines. inmune complexes and “all of those things”.
Clin Exp Allergy, 22 (1992), pp. 731-733
[17.]
B. Fox, T.B. Bull, A. Guz.
Mast cells in the human alveolar wall: an electronmicroscopic study.
J Clin Pathol, 34 (1981), pp. 1.333-1.342
[18.]
A.A. Irani, T.R. Bradford, C.E. Kepley, N.M. Seheehter, L.B. Schwartz.
Detection of MCT and MCTC types of human mast cells by immunohistochemistry using new monoclonal antitryptase and anti-chymase antibodies.
J Histochem Cytochem, 37 (1989), pp. 1.509-1.515
[19.]
K.C. Flint, K.B.P. Leung, B.N. Hudspith, J. Brostoff, F.L. Pearce, D. Geraint-James, et al.
Bronchoalveolar mast cells in sarcoidosis: increased numbers and accentuation of mediator release.
Thorax, 41 (1986), pp. 94-99
[20.]
O. Soler, S. Nioche, D. Valeyre, F. Basset, J. Benveniste, C. Burtin, et al.
Role of mast cells in the pathogenesis of hypersensitivitv pneumonitis.
Thorax, 42 (1987), pp. 565-572
[21.]
P.L. Haslam, A. Dewar, P. Butchers, Z.S. Primett, A. Newman-Taylor, M. Turner-Warwick.
Mast cells. atypical lymphocytes, and neutrophils in bronchoalveolar lavage in extrinsic allergic alveolitis. Comparison with other interstitial lung diseases.
Am Rev Respir Dis, 135 (1987), pp. 35-47
[22.]
A. Pesci, G. Bertorelli, D. Olivieri.
Mast cells in bronchoalveolar lavage fluid and in transbronchial biopsy specimens of patients with farmer's lung disease.
Chest, 100 (1991), pp. 1.197-1.202
[23.]
P.J. Haley, M. Schuley, K. Gott, T.B. Casale.
Mast cell hyperplasia in experimental hypersensitivity pneumonitis.
Int Arch Allergy Appl Immunol, 96 (1991), pp. 168-174
[24.]
H. Takizawa, K. Ohta, K. Hirai, Y. Misaki, T. Horiuchi, N. Kobayashi, et al.
Mast cells are important in the development of hypersensitivity pneumonitis. A study with mast-cell-deficient mice.
J Immunol, 143 (1989), pp. 1.982-1.988
[25.]
H.B. Richerson, L.I. Bernstein, J.N. Fink, G.W. Hunninghake, H.S. Novey, C.G. Reed.
Guidelines for the clinical evaluation of hypersensitivity pneumonitis.
J Allergy Clin Immunol, 84 (1989), pp. 839-844
[26.]
J.M. Sapage, J.L. Delgado, S. Torres, P. Vicente, J.C. Winck, P. Rodrigues, et al.
Suberose: contributo da lavagem broncoalveolar no diagnóstico da patologia respiratoria nos trabalhadores da industria da cortiça.
Arq SPPR, 9 (1992), pp. 321-327
[27.]
H.KlechW.Pohl. Technical recommendations and guidelines for bronchoalveolar lavage (BAL). Report of the European Society of Pneumology Task Group on BAL, 2 (1989), pp. 561-585
[28.]
A. Xaubet, J.A. Moisés, C. Agustí, J.A. Martos, C. Picado.
Identification of mast cells in bronchoalveolar lavage fluid. Comparison between different fixation and staining methods.
Allergy, 46 (1991), pp. 222-227
[29.]
S. Mönkäre, T. Haahtela.
Farmer's lung–a 5-years follow-up of eighty-six patients.
Clin Allergy, 17 (1987), pp. 143-151
[30.]
J. Rodrigues, J.P. Moreira da Silva, J.L. Delgado, M.G. Castel-Branco.
Pneumonites de hipersensibilidade.
Rev Port Imunoalergol, 1 (1992), pp. 34-49
[31.]
L. Delgado, J.C. Winck, J.M. Sapage, S. Torres, J. Moura e Sá, J.A. Fleming Torrinha.
Antibodies to Penicillium frequentans in cork worker's respiratory disease (suberosis). Application of the ImmunoCap IgG RAST in sera and bronchoalveolar lavage (BALF) measurements.
Proceedings of the XVI European Congress of Allergology and Clinical Immunology-ECACI’95., pp. 209-214
[32.]
A.F. Walls, J.A. Roberts, R.C. Godfrey, M.K. Church, S.T. Holgate.
Histochemical heterogeneity of human mast cells: disease-related differences in mast cell subsets recovered by bronchoalveolar lavage.
Int Arch Allergy Appl Immunol, 92 (1990), pp. 233-241
[33.]
R. Hastie, J.H. Heroy, D.A. Levy.
Basophil leukocytes and mast cells in human nasal secretions and scrapings studied by light microscopy.
Lab Invest, 40 (1979), pp. 554-561
[34.]
C. Ts’ao, R. Patterson, J.M. McKenna, I.M. Susko.
Ultrastructural identification of mast cells obtained from human bronchial lumens.
J Allergy Clin Immunol, 59 (1977), pp. 320-326
[35.]
O. Kawanami, V.J. Ferrans, J.D. Fulmer, R.G. Crystal.
Ultrastructural of pulmonary mast cells in patients with fibrotic lung disorders.
Lab Invest, 40 (1979), pp. 717-734
[36.]
S. Strobel, H.R.P. Miller, A. Ferguson.
Human intestinal mucosal mast cells: evaluation of fixation and staining techniques.
J Clin Pathol, 34 (1981), pp. 851-858
[37.]
F. Shanahan, I. McNiven, N. Dyck, J.A. Denburg, J. Bienenstock, A.D. Befus.
Human lung mast cells: distribution and abundance of histochemically distinct subpopulations.
Int Arch Allegy Appl Immunol, 83 (1987), pp. 329-331
[38.]
A.M. Irani, L.B. Schwartz.
Mast cell heterogeneity.
Clin Exp Allergy, 19 (1989), pp. 143-155
[39.]
B.E. Heard, A.J. Nunn, A.B. Kay.
Mast cells in human lungs.
J Pathol, 157 (1989), pp. 59-63
[40.]
T. Koshino, S. Teshima, N. Fukushima, T. Takaishi, K. Hirai, Y. Miyamoto, et al.
Identification of basophils by immunohistochemistry in the airways of post-mortem cases of fatal asthma.
Clin Exp Allergy, 23 (1993), pp. 919-925
[41.]
A. Pesci, G. Bertorelli, M. Gabrielli, D. Olivieri.
Mast cells in fibrotic lung disorders.
Chest, 103 (1993), pp. 989-996
[42.]
S.I. Rennard, M. Chafouri, A.B. Thompson, J. Linder, W. Vaughan, K. Jones, et al.
Fractional processing of sequential bronchoalveolar lavage to separate bronchial and alveolar samples.
Am Rev Respir Dis, 141 (1990), pp. 208-217
[43.]
S. Lam, J.C. Leriche, K. Kijek, D. Phillips.
Effect of bronchial lavage volume on cellular and protein recovery.
Chest, 88 (1985), pp. 856-859
[44.]
G. Semenzato, M. Chilosi, E. Ossi, L. Trentin, G. Pizzolo, A. Cipriani, et al.
Bronchoalveolar lavage and lung histology: comparative analysis of inflammatory and immnocompetent cells in patients with sarcoidosis and hypersensitivity pneumonitis.
Am Rev Respir Dis, 132 (1985), pp. 400-404
[45.]
F. Aldenbrog, K. Nilsson, B. Jarlshammar, L. Bjermer, L. Enerbäk.
Mast cells and biogenic amines in radiation-induced pulmonary fibrosis.
Am J Respir Cell Mol Biol, 8 (1993), pp. 112-117
[46.]
S.J. Galli.
New insights into “the riddle of the mast cells”: microenvironmental regulation of mast cell development and phenotypic hetrogeneity.
Lab Invest, 62 (1990), pp. 5-33
[47.]
M.M. Hamawy, S.E. Mergenhagen, R.P. Siraganian.
Adhesion molecules as regulators of mast-cell and basophil function.
Immunol Today, 15 (1994), pp. 62-66
[48.]
P. Valent.
The riddle of the mast cell: kit(CDl 17)-ligand as the missing link?.
Immunol Today, 15 (1994), pp. 111-114
[49.]
S.J. Galli, B.K. Wershil, J.J. Costa, M. Tsai.
For better or for worse: does stem cell factor importantly regulate mast cell function in pulmonary physiology and pathology?.
Am J Respir Cell Mol Biol, 11 (1994), pp. 644-645
[50.]
H.N. Claman.
Mast cells T cells and abnormal fibrosis.
Immunol Today, 6 (1985), pp. 192-195
[51.]
F. Levi-Schaffer, V. Segal, A. Nagler.
Mast cell and fibroblast functional activity are affected by immunocompetent cells in chronic graft vs host disease.
Int Arch Allergy Immunol, 99 (1992), pp. 238-241
[52.]
P.W. Askenase, H. Van Loveren.
Delayed-type hypersensitivity: activation of mast cells by antigen-specific T-cell factors initiates the Cascade of cellular interactions.
Immunol Today, 4 (1983), pp. 259-264
[53.]
H.A. Waldorf, L.J. Alsh, N.M. Schechter, G.F. Murphy.
Early cellular events in evolving cutaneous delayed hypersensitivity in humans.
Am J Pathol, 138 (1991), pp. 477-486
[54.]
A.M. Irani, S.S. Craig, G. DeBlois, C.O. Elson, N. Schechter, L.B. Schwartz.
Deficiency of the tryptase-positive, chymase-negative mast cell type in gastrointestinal mucosa of patients with detective T lymphocyte function.
J Immunol, 138 (1987), pp. 4.381-4.386
[55.]
E.J. Ruitenberg, A. Elgersma.
Absence of intestinal mast cell response in congenitally athymic mice during Trichinella spiralis infection.
Nature (Lond), 264 (1976), pp. 258-260
[56.]
B.E. Hol, F.H. Krouwels, B. Bruinier, R. Lutter, A. Bast, E.A. Wierenga, et al.
Heterogeneous effects of histamine on proliferation of lung and blood-derived T-cell clones from healthy and asthmatic persons.
Am J Respir Cell Mol Biol, 8 (1993), pp. 647-654
[57.]
M. Dohlsten, H.O. Sjógren, R. Carlsson.
Histamine acts directly on-human T cells to inhibit interleukin-2 and interferon-gamma production.
Cell Immunol, 109 (1987), pp. 65-74
[58.]
M. Shibata, D. Hoon, E. Okun, D. Morton.
Modulation of histamine type II receptors on CD8+ T cells by interleukin-2 and cimetidine.
Int Arch Allergy Immunol, 97 (1992), pp. 8-16
[59.]
J.V. Weinstock, S.W. Chensue, D.L. Boros.
Modulation of granulomatous hypersensitivity, V. participation of histamine positive and negative lymphocytes in the granulomatous response of Schistosoma mansoni-infected mice.
J Immunol, 130 (1983), pp. 423-427
[60.]
A. Teles Araújo, J. Valença, A.B. Almeida, M.F. Costa.
Release of histamine by cultures of broncho-alveolar adherente cells.
pp. 35-42
[61.]
D.H. Broide, C.M. Smith, S.I. Wasserman.
Mast cells and pulmonary fibrosis. Identification of a histamine releasing factor in bronchoalveolar lavage fluid.
J Immunol, 145 (1990), pp. 1.838-1.844
[62.]
M.C. Liu, C. Proud, L.M. Lichtenstein, D.W. McGlashan, R.P. Schleimer, N.F. Adkinson, et al.
Human lung macrophage-derived histamin-releasing activity is due to IgE-dependent factors.
J Immunol, 136 (1986), pp. 2.588-2.595
[63.]
R.M. Cherniak.
Physiologic alterations in intersticial lung disease.
Intersticial lung disease, pp. 79-90
[64.]
L. Bjermer, A. Engström-Laurent, R. Lundgren, L. Rosenhall, R. Hällgren.
Bronchoalveolar mastocytis in farmer's lung is related to disease activity.
Arch Intern Med, 148 (1988), pp. 1.362-1.365
Copyright © 1999. Sociedad Española de Neumología y Cirugía Torácica
Archivos de Bronconeumología
Article options
Tools

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