A protective role for T lymphocytes in asbestos-induced pulmonary inflammation and collagen deposition

Our plain-English summary of A protective role for T lymphocytes in asbestos-induced pulmonary inflammation and collagen deposition, by E. Corsini, M.I. Luster, J. Mahler, et al (American Journal of Respiratory Cell and Molecular Biology, 1994).

The study

• Authors: E. Corsini, M.I. Luster, J. Mahler, W.A. Craig, M.E. Blazka, G.J. Rosenthal
• Journal: American Journal of Respiratory Cell and Molecular Biology
• Published: 1994;11(5):531-9
• Cited by: 34 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Several lines of evidence have suggested that specific (i.e., lymphocyte) immunity plays a role in chemical-induced pulmonary diseases, including asbestosis. To evaluate the influence of cell-mediated immunity in pulmonary inflammation and fibrosis evoked by asbestos fibers, we compared the effects of asbestos in immunodeficient mice (Balb/c nu/nu and severe combined immunodeficient [C3H-SCID]), immunologically normal mice of the same genetic background, and immunodeficient mice reconstituted with syngeneic T lymphocytes. Increases in lavaged cell numbers occurred in asbestos-treated immunodeficient mice compared with asbestos-treated immunocompetent or immunodeficient mice that received T lymphocytes. Differential analysis of the collected cells in treated mice demonstrated a predominantly neutrophilic infiltrate that correlated with increased levels of leukotriene B4 and prostaglandin E2. There were no significant differences between immunocompetent and athymic asbestos-treated mice in bronchoalveolar lavaged total protein. However, asbestos-treated SCID mice revealed a significant increase in protein content and lactate dehydrogenase activity compared with asbestos-treated normal mice, which did not occur in T lymphocyte-reconstituted SCID mice. Fibronectin levels were elevated in asbestos-exposed athymic mice when compared with air-exposed athymic mice or asbestos-exposed immunocompetent mice. Both asbestos-treated athymic and SCID mice showed a significant increase in total lung hydroxyproline when compared with asbestos-treated immunocompetent mice. Lung hydroxyproline was also reduced in asbestos-exposed SCID mice after T lymphocyte reconstitution and, conversely, increased in T cell-depleted Balb/c mice.(ABSTRACT TRUNCATED AT 250 WORDS)

In plain English

This was an animal experiment. Mice lacking T lymphocytes (athymic Balb/c nu/nu mice and C3H SCID mice), normal mice of the same strains, and SCID mice given lymphocytes or T cells from normal mice inhaled chrysotile asbestos for 3 to 5 days. Control mice breathed room air. Six weeks after exposure, cell counts in lung-wash fluid rose about 2-fold in normal C3H mice and about 4-fold in SCID mice. Giving SCID mice lymphocytes prevented much of this increase. Lung hydroxyproline, a measure of collagen, averaged 482.9 micrograms per lung in asbestos-exposed SCID mice versus 280.8 in asbestos-exposed normal mice, and was only partly reduced by giving lymphocytes. Under the microscope, collagen deposition appeared in 8 of 8 asbestos-exposed SCID mice and 4 of 9 normal mice. Removing T cells from normal Balb/c mice raised hydroxyproline further, but this change (P = 0.058) did not reach the study's significance level. The authors concluded that T cells limit asbestos-induced lung inflammation and fibrosis, consistent with a protective role in asbestosis.

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: Animal experiment (inhalation exposure of immunodeficient, normal, and immune-reconstituted mice; rat lung tissue used for gene-expression analysis)
• Who was studied: Mice aged 10 to 11 weeks: Balb/c nu/+ (normal) and Balb/c nu/nu (athymic, T cell-deficient), C3H (normal) and C3H SCID (severe combined immunodeficient), SCID mice reconstituted with splenic lymphocytes (SCID-L) or T cells (SCID-T), and Balb/c mice depleted of T cells by antibody. Group sizes were mostly 3 to 10 animals. Fisher 344 rats were used for the interferon-gamma mRNA analysis.
• Exposure: Inhaled NIEHS chrysotile asbestos (Plastibest 20) aerosol, 3 hours per day for 3 consecutive days (nude mouse studies) or 4 hours per day for 5 consecutive days (SCID studies); controls breathed room air
• Main results:
  • Six weeks after exposure, cell numbers in lung-wash fluid increased 2-fold in asbestos-exposed normal C3H mice and 4-fold in asbestos-exposed SCID mice
  • Giving SCID mice splenic lymphocytes or T lymphocytes from normal mice prevented much of the asbestos-related increase in lung-wash cell numbers
  • In immunodeficient mice, the number of neutrophils (PMNs) stayed raised 12 weeks after exposure, while the neutrophil response in normal mice had resolved
  • Six weeks after exposure, lung hydroxyproline was 482.9 plus or minus 22.5 micrograms per lung in asbestos-exposed SCID mice versus 280.8 plus or minus 15.7 in asbestos-exposed C3H mice. Reconstitution brought protein and LDH down to levels comparable to normal mice, but reduced hydroxyproline only partly (387.8 in SCID-L, 413.5 in SCID-T).
  • Collagen deposition on microscopy, 6 weeks after exposure: 4/9 asbestos-exposed C3H mice (severity 1.0), 8/8 asbestos-exposed SCID mice (severity 2.1), 10/10 SCID-L and 8/8 SCID-T mice (severity 1.2 each); none in air-exposed mice. Lymphocyte reconstitution did not reduce the incidence.
  • In asbestos-exposed Balb/c mice depleted of T cells, lung hydroxyproline was further increased, with P = 0.058
  • One week after exposure, athymic mice had significantly higher LTB4 and PGE2 in lung-wash fluid than air-exposed athymic mice; the increase in normal mice was slight and not statistically significant
  • Fibronectin in lung-wash fluid rose significantly in asbestos-exposed athymic mice within 1 week; the rise in normal mice was slight and not significant
  • Interferon-gamma mRNA was undetectable in rat lung tissue even after 40 PCR cycles
• The authors' conclusion: The authors concluded that T cells influence asbestos-induced lung damage by minimizing both inflammatory and fibrotic responses, consistent with a protective role for T lymphocytes in asbestosis
• Limitations the authors state:
  • Hydroxyproline measures collagen content but cannot tell new collagen deposited outside cells from collagen inside a larger number of fibroblasts
  • Interferon-gamma may be expressed at time points the authors did not examine
  • Whether T cells act directly on these responses was not determined
  • Whether impaired cell-mediated immunity in asbestos-exposed people predisposes them to fibrosis remains to be determined

Topics

The National Library of Medicine indexes this study under subjects our site covers: Asbestosis, Chrysotile.

Medical terms in this study, explained in our Lexicon: Inflammation, Collagen, Deposition, Fibrosis, Lactate Dehydrogenase (LDH).

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