Perforin, granzyme B, and FasL expression by peripheral blood T lymphocytes in emphysema

Respir Res. 2007 Sep 6;8(1):62. doi: 10.1186/1465-9921-8-62.

Abstract

Background: It is generally accepted that emphysematous lungs are characterized by an increase in the numbers of neutrophils, macrophages, and CD8+ T lymphocytes, the lasts having increased cytotoxic activity. Because systemic inflammation is also a component of emphysema, we hypothesize that peripheral CD8+ T lymphocytes of emphysematous smokers who show evidence of systemic inflammation will have higher expression of cytotoxic molecules.

Methods: We assessed parameters of systemic inflammation in normal individuals (smokers or non-smokers) and in emphysematous subjects with an active smoking history by measuring serum interleukine-6, C-reactive protein, and tumor necrosis factor. Expression of perforin, granzyme B, and FasL protein by CD8+ T lymphocytes, CD4+ T lymphocytes, and natural killer cells were assessed by flow cytometry while perforin, granzyme B, and FasL mRNA expression were measured on purified systemic CD8+ T lymphocytes by real-time PCR.

Results: Emphysematous smokers had higher levels of serum interleukine-6 than normal subjects. Even with the presence of systemic inflammation in emphysematous smokers, the percentage of peripheral CD8+ T lymphocytes, CD4+ T lymphocytes, and NK cells expressing perforin and granzyme B protein was not different between the three groups.

Conclusion: Despite evidence of systemic inflammation, peripheral T lymphocytes of emphysematous smokers did not show higher levels of cytotoxic markers, suggesting that increase of activated T lymphocytes in the emphysematous lung may be due to either activation in the lung or specific peripheral recruitment.

Publication types

  • Comparative Study

MeSH terms

  • Fas Ligand Protein / biosynthesis*
  • Fas Ligand Protein / blood
  • Fas Ligand Protein / genetics
  • Female
  • Gene Expression Regulation / physiology
  • Granzymes / biosynthesis*
  • Granzymes / blood
  • Granzymes / genetics
  • Humans
  • Male
  • Middle Aged
  • Perforin / biosynthesis*
  • Perforin / blood
  • Perforin / genetics
  • Pulmonary Emphysema / blood*
  • Pulmonary Emphysema / enzymology
  • Pulmonary Emphysema / genetics
  • Smoking / blood
  • Smoking / genetics
  • Smoking / immunology
  • T-Lymphocytes / enzymology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*

Substances

  • Fas Ligand Protein
  • Perforin
  • Granzymes