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


CONCLUSIONS
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.
Morissette
Mathieu C
MC
Hôpital Laval, Institut de cardiologie et de pneumologie, Québec, Qc, Canada. mathieu.morissette@crhl.ulaval.ca
Parent
Julie
J
Milot
Julie
J
D053222:Fas Ligand Protein / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D053804:Granzymes / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D054353:Perforin / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D011656:Pulmonary Emphysema / Q000097:blood* / Q000201:enzymology / Q000235:genetics; D012907:Smoking / Q000097:blood / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*