Increases in collagen type I synthesis in asthma: the role of eosinophils and transforming growth factor-beta.
BACKGROUND
Collagen type I is one of the major deposits in thickening of the reticular basement membrane of asthma.


OBJECTIVE
In this study, we assessed turnover of collagen type I in asthma by measuring procollagen type I C-terminal peptide (PICP) and collagen type I C-terminal telopeptide (ICTP) in induced sputum.


RESULTS
PICP but not ICTP was found to be significantly higher in asthma subjects than in normal volunteers (P < 0.05). In asthma, PICP was inversely correlated with %FEV(1.0) (r = -0.539), and its levels significantly increased upon exacerbation (P < 0.05), indicating that collagen synthesis increases during asthma exacerbation. Additionally, PICP was found to significantly correlate with eosinophil counts in sputum (r = 0.539), indicating that eosinophils stimulate collagen turnover. Because eosinophils can produce TGF-beta, a potent stimulator of collagen synthesis, we immunocytochemically examined TGF-beta-positive cells in sputum. TGF-beta-positive cells significantly correlated with eosinophil counts (r = 0.811) and PICP (r = 0.569), suggesting that TGF-beta released from eosinophils is involved in collagen synthesis.


CONCLUSIONS
The results of the present study suggest that collagen synthesis is stimulated in asthmatic airways by eosinophils through TGF-beta, while collagen degradation is not, and that PICP in sputum can act as a new marker for airway inflammation in asthma.
Nomura
A
A
Department of Pulmonary Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Uchida
Y
Y
Sakamoto
T
T
Ishii
Y
Y
Masuyama
K
K
Morishima
Y
Y
Hirano
K
K
Sekizawa
K
K
D001249:Asthma / Q000378:metabolism* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D024042:Collagen Type I / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000502:physiology; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D007120:Immunochemistry; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000378:metabolism*; D010455:Peptides; D011347:Procollagen / Q000096:biosynthesis* / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism; D013183:Sputum / Q000737:chemistry / Q000378:metabolism; D013223:Statistics as Topic; D016212:Transforming Growth Factor beta / Q000502:physiology
D015415:Biomarkers; D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; D012709:Serum Albumin; D016212:Transforming Growth Factor beta; C052929:collagen type I trimeric cross-linked peptide; C042813:procollagen type I carboxy terminal peptide