Additional proteins in BAL fluid of Metsovites environmentally exposed to asbestos: more evidence of "protection" against neoplasia?

Our plain-English summary of Additional proteins in BAL fluid of Metsovites environmentally exposed to asbestos: more evidence of "protection" against neoplasia?, by V. Galani, S. Constantopoulos, C. Manda-Stachouli, et al (Chest, 2002).

The study

• Authors: V. Galani, S. Constantopoulos, C. Manda-Stachouli, M. Frangou-Lazaridis, A. Mavridis, M. Vassiliou, Y. Dalavanga
• Journal: Chest
• Published: 2002;121(1):273-8
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Inhabitants of Metsovo in northwest Greece have been exposed to asbestos from use of a tremolite-containing whitewash ("luto" soil). As a result, they have increased incidence of malignant pleural mesothelioma and pleural calcifications (PCs). However, subjects with calcifications have a much lower incidence of mesothelioma than those without. A previous study of the two groups with BAL revealed higher proportional lymphocytosis among subjects with calcifications. We suggested that BAL lymphocytosis may be somehow correlated with "protection" against neoplasia.

Methods: The present report is a study of the liquid phase of BAL in the two groups. BAL specimens of 43 Metsovites (13 subjects with PCs and 30 subjects without PCs) and two control groups were examined. We measured total protein, albumin, IgG, IgA, and interleukin-6. Proteins were analyzed with sodium dodecyl sulfate-polyacrylamide gel electrophoresis and two-dimensional electrophoresis and further characterized using an appropriate computer program.

Results: The most interesting finding was the presence of two additional protein spots corresponding to the electrophoretic site of Ig heavy chain and C(4) component of complement. The two proteins were present in all Metsovites with PCs but in none without PCs and also in none of the control groups.

Conclusion: This study further separates two groups of Metsovites with different reaction to asbestos, possibly as a result of different activation of alveolar macrophages. This difference leads the first group to the formation of PCs, BAL fluid lymphocytosis, and relative "protection" against malignancy, and the second group to no calcifications, no lymphocytosis, but also no protection against malignancy.

In plain English

This laboratory study analyzed lung-washing (bronchoalveolar lavage) fluid from 43 residents of Metsovo, northwest Greece, who had been exposed since childhood to asbestos from a tremolite-containing whitewash ("luto" soil). Thirteen had pleural calcifications on chest X-ray and 30 did not. The 30 included 5 patients with malignant pleural mesothelioma and 5 with bronchogenic carcinoma. Two five-person control groups were studied: primary Sjögren's syndrome patients, and non-Metsovites with pleural calcifications from other causes. Two-dimensional gel electrophoresis showed two additional protein spots in every Metsovite with calcifications, but in none without calcifications and in neither control group. A computer program matched them to immunoglobulin heavy chain and complement component C4. Total protein was lowest in Metsovites without calcifications. Albumin, IgG and IgA did not differ significantly between the Metsovite groups, nor did interleukin-6 across them and the Sjögren's patients. The authors concluded that the groups react differently to asbestos, possibly through activated alveolar macrophages, a hypothesis they said needs confirmation. They linked calcifications to a relative "protection" against cancer that they had suggested in earlier work; this study did not measure cancer rates.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Cross-sectional laboratory comparison of the liquid phase of bronchoalveolar lavage (BAL) fluid between groups (protein assays and one- and two-dimensional gel electrophoresis)
• Who was studied: 43 inhabitants of the Metsovo area, northwest Greece: 13 with pleural calcifications (PCs) on chest radiography and 30 without PCs. The 30 without PCs included 5 patients with malignant pleural mesothelioma and 5 with bronchogenic carcinoma; the other 33 subjects were volunteers. Controls were 5 patients with primary Sjögren's syndrome and BAL fluid lymphocytosis, and 5 non-Metsovites with extensive PCs from causes other than asbestos (2 hemothorax, 3 presumably previous tuberculous pleurisy). Study dates are not given.
• Exposure: Environmental (non-occupational) exposure since childhood to asbestos from a tremolite-containing whitewash ("luto" soil); no dose measurements reported
• Main results:
  • Two additional protein spots appeared on two-dimensional electrophoresis in every Metsovite with PCs (13 subjects). One was at a molecular weight of 55 kd, pI 7.0 to 7.5; the other at 34 kd, pI 6.2.
  • The two additional spots were never seen in any Metsovite without PCs (30 subjects) or in any patient in either control group.
  • Computer matching against a reference map placed the two spots at the positions of immunoglobulin heavy chain and the C4 component of complement.
  • Total protein differed significantly among the three groups and was lowest in Metsovites without PCs. Table 2 gives means (with standard deviations) in micrograms per milliliter: 58.80 (23.61) without PCs, 110.70 (24.37) with PCs, and 261.20 (91.89) in Sjögren's syndrome patients.
  • Albumin, IgG and IgA in BAL fluid did not differ statistically significantly between the two Metsovite groups. All values were higher in Sjögren's syndrome patients (data not shown).
  • Interleukin-6 did not differ significantly among the three groups compared: Metsovites with PCs, Metsovites without PCs, and Sjögren's syndrome patients. It was lower in Metsovites with PCs. Means in Table 2 were 17.90 pg/mL with PCs, 24.30 pg/mL without PCs, and 28.50 pg/mL in Sjögren's syndrome patients. It was not measured in the second control group.
  • One-dimensional (SDS) electrophoresis showed no differences in protein profile between the two Metsovite groups.
• The authors' conclusion: The authors concluded that the results further separate Metsovites into two groups with different types and degrees of reaction to the fiber. In their view, the group with PCs shows proportional BAL lymphocytosis, the additional proteins and relative protection against neoplasia, while the other group shows none of these. They suggested both proteins could be attributed to activated alveolar macrophages. The protection against neoplasia rests on their previous study, not on cancer data collected here.
• Limitations the authors state:
  • Heavy chain Ig and C4 are not produced only under alveolar macrophage control, and macrophage activation has other effects not seen in this population, so the macrophage hypothesis needs confirmation in specific studies.
  • Comparison with an earlier study of asbestos-exposed patients that found other protein spots was difficult, mainly because of differences in terminology.
  • Study of the second control group (non-Metsovites with PCs) was limited to protein analysis for additional proteins.
  • Whether the findings apply to other environmentally or occupationally exposed populations would need a large study.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Asbestosis, Mesothelioma, Pleural plaques and thickening, Tremolite.

Medical terms in this study, explained in our Lexicon: BAL Fluid, Tremolite, Whitewash, Luto, Pleural Mesothelioma, Pleural Calcification, Mesothelioma, Alveolar Macrophage.

Related studies

• Lymphocytic alveolitis and pleural calcifications in nonoccupational asbestos exposure. Protection against neoplasia? — S.H. Constantopoulos, Y.A. Dalavanga, et al. (1992)
• Decreasing prevalence of pleural calcifications among Metsovites with nonoccupational asbestos exposure — C. Manda-Stachouli, Y. Dalavanga, et al. (2004)
• Metsovo lung outside Metsovo. Endemic pleural calcifications in the ophiolite belts of Greece — S.H. Constantopoulos, P. Theodoracopoulos, et al. (1991)
• Two dimensional protein patterns of bronchoalveolar lavage fluid from non-smokers, smokers, and subjects exposed to asbestos — M. Lindahl, T. Ekström, et al. (1996)
• Proteome analysis of bronchoalveolar lavage in individuals from Metsovo, nonoccupationally exposed to asbestos — D.T. Archimandriti, Y.A. Dalavanga, et al. (2009)
• Tremolite whitewashing and pleural calcifications — S.H. Constantopoulos, N.A. Saratzis, et al. (1987)

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