Increased levels of vascular endothelial growth factor in induced sputum in asthmatic patients

被引:141
作者
Asai, K [1 ]
Kanazawa, H [1 ]
Kamoi, H [1 ]
Shiraishi, S [1 ]
Hirata, K [1 ]
Yoshikawa, J [1 ]
机构
[1] Osaka City Univ, Dept Resp Med, Grad Sch Med, Abeno Ku, Osaka 5458585, Japan
关键词
beclomethasone dipropionate; bronchial asthma; extravasation; induced sputum; vascular endothelial growth factor;
D O I
10.1046/j.1365-2222.2003.01576.x
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background Vascular endothelial growth factor (VEGF) is highly expressed in the airway of asthmatic patients. As VEGF increases airway vascular permeability, consequent thickening of the airway wall mucosa may lead to narrowing of the airway lumen. Objective We evaluated the relationship between VEGF levels in induced sputum and eosinophilic inflammatory profiles, and the degree of airway vascular permeability in asthmatic patients and we evaluated the effect of inhaled corticosteroids on VEGF levels in induced sputum. Methods Induced sputum specimens were obtained from 28 glucocorticosteroids free asthmatics and 11 healthy control subjects. We examined VEGF levels and airway vascular permeability index in induced sputum. After the initial sputum induction, 21 asthmatics received 8-week inhaled beclomethasone dipropionate (BDP, 800 mug/day) therapy, then sputum induction was repeated. Results The VEGF levels in asthmatics were significantly higher than in healthy control subjects (P < 0.0001). The VEGF levels were negatively correlated with forced expiratory volume of 1 s (FEV1, % predicted, r = - 0.68, P < 0.001), the percentage of eosinophils (r = 0.51, P < 0.01) and ECP levels (r = 0.39, P < 0.05). Moreover, the VEGF levels were significantly correlated with airway vascular permeability index (r = 0.61, P < 0.001). After 8-week inhaled BDP therapy, the VEGF levels were significantly decreased compared to pretreatment levels (P < 0.0001) and the VEGF levels were significantly correlated with airway vascular permeability index even in post-treatment asthmatics (r = 0.62, P < 0.01). Conclusion The VEGF levels in induced sputum were increased in asthmatics and its levels were associated with degree of airway narrowing and airway vascular permeability. These findings provide strong evidence that VEGF may play an important role in the pathogenesis of bronchial asthma.
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页码:595 / 599
页数:5
相关论文
共 23 条
[1]  
[Anonymous], 1987, AM REV RESPIR DIS, V136, P225
[2]   Budesonide reduces vascular endothelial growth factor secretion and expression in airway (Calu-1) and alveolar (A549) epithelial cells [J].
Bandi, N ;
Kompella, UB .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2001, 425 (02) :109-116
[3]   Mast cells can secrete vascular permeability factor vascular endothelial cell growth factor and exhibit enhanced release after immunoglobulin E-dependent upregulation of Fcε receptor I expression [J].
Boesiger, J ;
Tsai, M ;
Maurer, M ;
Yamaguchi, M ;
Brown, LF ;
Claffey, KP ;
Dvorak, HF ;
Galli, SJ .
JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 188 (06) :1135-1145
[4]   VEGF induces airway epithelial cell proliferation in human fetal lung in vitro [J].
Brown, KRS ;
England, KM ;
Goss, KL ;
Snyder, JM ;
Acarregui, MJ .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2001, 281 (04) :L1001-L1010
[5]  
Demoly P, 1999, CLIN EXP ALLERGY, V29, P1390
[6]  
DVORAK HF, 1995, AM J PATHOL, V146, P1029
[7]   Vascular endothelial growth factor induces endothelial fenestrations in vitro [J].
Esser, S ;
Wolburg, K ;
Wolburg, H ;
Breier, G ;
Kurzchalia, T ;
Risau, W .
JOURNAL OF CELL BIOLOGY, 1998, 140 (04) :947-959
[8]  
Fehrenbach H, 1999, ANAT REC, V254, P61
[9]   Expression of vascular endothelial growth factor by human eosinophils: Upregulation by granulocyte macrophage colony-stimulating factor and interleukin-5 [J].
Horiuchi, T ;
Weller, PF .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1997, 17 (01) :70-77
[10]   Expression of vascular endothelial growth factor, basic fibroblast growth factor, and angiogenin immunoreactivity in asthmatic airways and its relationship to angiogenesis [J].
Hoshino, M ;
Takahashi, M ;
Aoike, N .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2001, 107 (02) :295-301