Upregulation of alpha GM-CSF-receptor in nonatopic asthma but not in atopic asthma.
BACKGROUND
Intrinsic asthma is characterized by an increased number of activated eosinophils and macrophages and an increased expression of the hematopoietic growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) in the bronchial mucosa.


OBJECTIVE
This study was carried out to investigate the expression of alpha GM-CSF receptor (alpha GM-CSFr) messenger RNA and protein in the bronchial mucosa of patients with intrinsic or atopic asthma and of control subjects and to correlate the expression of alpha GM-CSFr to the number of EG2+ cells (eosinophils) and CD68+ cells (macrophages) and pulmonary function.


METHODS
Nineteen patients with stable asthma (9 with atopic and 10 with intrinsic asthma) and 22 normal control subjects (12 atopic and 10 nonatopic subjects) were recruited, and FEV1 (percent predicted) and PC20 were measured before bronchoscopy. Endobronchial biopsy specimens were obtained and examined for membrane-bound alpha GM-CSFr by using in situ hybridization and immunocytochemistry.


RESULTS
alpha GM-CSFr mRNA- and protein-positive cells were identified in biopsy specimens from all four groups studied. There was no significant difference in the number of cells expressing alpha GM-CSFr mRNA and protein in patients with atopic asthma compared with atopic and nonatopic control subjects. However, the numbers of alpha GM-CSFr mRNA- and protein-positive cells were significantly higher in nonatopic patients with asthma compared with atopic patients with asthma and atopic and nonatopic control subjects (p < 0.001). In the patients with intrinsic asthma, the number of alpha GM-CSFr mRNA-positive cells per millimeter of basement membrane correlated with numbers of CD68+ cells (r2 = 0.87, p < 0.001) but not with EG2+ cells, and colocalization studies demonstrated that 80% of the cells expressing alpha GMCSFr mRNA were CD68+. The expression of GM-CSF was also significantly increased in patients with intrinsic asthma compared with those with atopic asthma and control subjects (p < 0.05). In addition, in intrinsic asthma, there was a correlation between alpha GM-CSFr mRNA and FEV1 (r2 = 0.61, p < 0.05).


CONCLUSIONS
These results demonstrate that elevated numbers of cells expressing alpha GM-CSFr can be detected in nonatopic asthma but not in atopic asthma and suggest that this increased expression is predominantly macrophage-associated and may play an important pathophysiologic role in intrinsic asthma.
Kotsimbos
A T
AT
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
Humbert
M
M
Minshall
E
E
Durham
S
S
Pfister
R
R
Menz
G
G
Tavernier
J
J
Kay
A B
AB
Hamid
Q
Q
D000328:Adult; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001249:Asthma / Q000378:metabolism*; D001485:Basement Membrane / Q000166:cytology; D001706:Biopsy; D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D005541:Forced Expiratory Volume; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000378:metabolism*; D017403:In Situ Hybridization; D008264:Macrophages / Q000145:classification / Q000166:cytology; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D012333:RNA, Messenger; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; C067980:CD68 antigen, human; D000097382:CD68 Molecule