Evaluation of apoptosis of eosinophils, macrophages, and T lymphocytes in mucosal biopsy specimens of patients with asthma and chronic bronchitis.
BACKGROUND
Apoptosis regulates inflammatory cell survival, and its reduction contributes to the chronicity of an inflammatory process. Apoptosis is controlled by suppressing or inducing genes, such as bcl-2 and p53, respectively.


OBJECTIVE
We sought to assess apoptosis of eosinophils, macrophages, and T lymphocytes in bronchial biopsy specimens from asthmatic subjects and to examine its regulation by evaluating the expression of B-cell lymphoma leukemia-2 (Bcl-2) and P53 proteins. We also sought to explore the relationships between cell apoptosis and GM-CSF, a cytokine able to increase eosinophil and macrophage survival.


METHODS
Apoptosis in eosinophils, macrophages, and T lymphocytes was evaluated in bronchial biopsy specimens obtained from 30 asthmatic subjects, 26 subjects with chronic bronchitis, and 15 control subjects by combining the terminal deoxynucleotidyl transferase-mediated dNTP nick end-labeling technique and immunohistochemistry. The expression of P53, Bcl-2, and GM-CSF was studied through immunohistochemistry by using specific mAbs.


RESULTS
The number of apoptotic eosinophils and macrophages was lower in subjects with asthma than in those with chronic bronchitis (P <.007 and P <.001, respectively) and inversely correlated with the clinical severity of asthma (P <.001 and P <.002, respectively). Few T lymphocytes were apoptotic in all groups studied. In asthma GM-CSF+ cells correlated with the number of nonapoptotic eosinophils and macrophages (P =.0001) and with the severity of the disease (P <.003). In asthma Bcl-2+ cells were higher than in control subjects and subjects with chronic bronchitis (P <.002 and P <.015, respectively), they outnumbered P53+ cells, and they correlated with the number of T lymphocytes (P <.001) and with the severity of the disease (P <.003).


CONCLUSIONS
Airway inflammation in asthma is associated with an enhanced survival of different cell types caused by reduced apoptosis.
Vignola
A M
AM
Istituto di Fisiopatologia Respiratoria, C.N.R., Via Trabucco, Palermo, Italy.
Chanez
P
P
Chiappara
G
G
Siena
L
L
Merendino
A
A
Reina
C
C
Gagliardo
R
R
Profita
M
M
Bousquet
J
J
Bonsignore
G
G
D000328:Adult; D017209:Apoptosis; D001249:Asthma / Q000473:pathology / Q000503:physiopathology*; D001706:Biopsy; D001980:Bronchi / Q000473:pathology*; D001991:Bronchitis / Q000473:pathology / Q000503:physiopathology*; D018955:CD36 Antigens / Q000096:biosynthesis; D002908:Chronic Disease; D004804:Eosinophils / Q000502:physiology*; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008264:Macrophages / Q000502:physiology*; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
D018955:CD36 Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D016178:Granulocyte-Macrophage Colony-Stimulating Factor