Effects of Chronic Aspergillus Fumigatus Exposure on Epithelial Cell Injury and Expression of Epidermal Growth Factor Receptor in Airways of Asthmatic Rats_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

GAO Fusheng , JIN Xianqiao , QIAO Jianou , ZHANG Yi.

Department of Respiratory Medicine, Shanghai First People’s Hospital Affiliated to Shanghai Jiaotong Univerisity. Shanghai, 200080, ChinaCorresponding Author: JIN Xian-qiao, E-mail: jinxianqiao@ 126. com;

Corresponding author：

Keywords：

Asthma; Aspergillus fumigatus; Epidermal growth factor receptor; Airway epithelial cell

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To explore the effects of prolonged inhalation of Aspergillus fumigatus ( Af)spores on epithelial cell injury and expression of epidermal growth factor receptor( EGFR) in airways of asthmatic rats. Methods 64 male Wistar rats were randomly divided into 8 groups, ie. chronic asthma group ( group A) , chronic asthma plus Af spores inhalation for 1 week ( group B) , 3 weeks ( group C) and 5 weeks ( group D) , chronic asthma plus saline inhalation for 5 weeks ( group E) , OVA-sensitized and salinechallenged group ( group F) , and OVA-sensitized and saline-challenged plus Af spores inhalation for 5 weeks ( group G) ( each n =8) . The airway resistance ( Raw) and change of Raw after acetylcholine provocation were detected using a computerized system. The concentrations of epidermal growth factor ( EGF) and
transforming growth factor alpha( TGF-α) in BALF were measured by ELISA. The extents of epithelial cell injury and goblet cell hyperplasia were evaluated on hematoxylin and eosin-stained( HE) and periodic acidschiff ( PAS) stained lung sections. The expression of EGFR in airway epithelia was demonstrated by
immunohistochemistry, and the level of EGFR protein in the rat lung tissues was measured by western blot.Results The concentration of EGF( pg/mL) ( 51. 72 ±8. 54, 68. 12 ±7. 85, 86. 24 ±9. 12, respectively)and TGF-α( pg/mL) ( 55. 26 ±9. 30, 75. 58 ±11. 56, 96. 75 ±14. 66, respectively) , detached/ inner perimeter of epithelium( % ) ( 11. 25 ±3. 12, 26. 45 ±5. 56, 28. 50 ±7. 50, respectively) , the ratio of goblet cell area to epithelial cell area ( % ) ( 16. 42 ±5. 24, 22. 64 ±6. 82, 36. 38 ±9. 21, respectively) , the integrated optical density ( IOD) of EGFR positive stain in airway epithelial cells ( 82 ±15,120 ±19, 165 ±21, respectively) , and the EGFR protein levels in lung tissues ( 0. 91 ±0. 26, 1. 61 ±0. 52, 2. 52 ±0. 78,respectively) in group B, C, and D were higher than those in group A, E, F and G( P lt; 0. 05 or P lt;0. 01) .
The change rates of Raw( % ) ( 61. 91 ±5. 26, 84. 69 ±6. 38) in group C and D were higher than those in group A, E, F and G ( P lt; 0. 05 or P lt;0. 01) . The IOD of EGFR was positively correlated with detached/inner perimeter of epithelium( % ) and the ratio of goblet cell area to epithelial cell area( % ) ( r = 0. 692,P lt;0. 01; r = 0. 657, P lt; 0. 01, respectively) . Conclusion Prolonged inhalation of Aspergillus fumigatus spores can aggravate airway epithelial cell injury, up-regulate the expression of EGFR in airway epithelial cell and induce goblet cell hyperplasia, thus increase the airway responsiveness in rats with chronic asthma.

Citation： GAO Fusheng,JIN Xianqiao,QIAO Jianou,ZHANG Yi.. Effects of Chronic Aspergillus Fumigatus Exposure on Epithelial Cell Injury and Expression of Epidermal Growth Factor Receptor in Airways of Asthmatic Rats. Chinese Journal of Respiratory and Critical Care Medicine, 2010, 9(2): 115-121. doi: Copy

1.	Burgel PR，Nadel JA. Roles of epidermal growth factor receptor activation in epithelial cell repair and mucin production in airway epithelium. Thorax，2004，59：992-996.
2.	Puddicombe SM，Polosa R，Richter A，et al. Involvement of the epidermal growth factor receptor in epithelial repair in asthma. FASEB J，2000，14：1362-1374.
3.	Denning DW，O’Driscoll BR，Hogaboam CM，et al. The link between fungi and severe asthma：a summary of the evidence. Eur Respir J，2006，27：615-626.
4.	Gao FS，Qiao JO，Zhang Y，Jin XQ. Chronic intranasal administration of Aspergillus fumigatus spores leads to aggravation of airway inflammation and remodeling in asthmatic rats. Respirology，2009，14：360-370.
5.	Palmans E，Kips JC，Pauwels RA. Prolonged allergen exposure induces structural airway changes in sensitized rats. Am J Respir Crit Care Med，2000，161：627-635.
6.	高福生，龙飞，祁卉卉，等. 反复吸入烟曲霉孢子对慢性阻塞性肺疾病大鼠气道炎症和重构的影响. 中国呼吸和危重监护杂志，2008，7：205-209.
7.	Glaab T，Mitzner W，Braun A，et al. Repetitive measurements of pulmonary mechanics to inhaled cholinergic challenge in spontaneously breathing mice. J Appl Physiol，2004，97：1104-1111.
8.	Sumi Y，Foley S，Daigle S，et al. Structural changes and airway remodelling in occupational asthma at a mean interval of 14 years after cessation of exposure. Clin Exp Allergy，2007，37：1781-178.
9.	Snibson KJ，Bischof RJ，Slocombe RF，et al. Airway remodelling and inflammation in sheep lungs after chronic airway challenge with house dust mite. Clin Exp Allergy，2005，35：146-152.
10.	Leigh R，Ellis R，Wattie J，et al. Dysfunction and remodeling of the mouse airway persist after resolution of acute allergen-induced airway inflammation. Am J Respir Cell Mol Biol，2002，27：526-535.
11.	Ou XM，Feng YL，Wen FQ，et al. Macrolides attenuate mucus hypersecretion in rat airways through inactivation of NF-?B. Respirology，2008，13：63-72.
12.	Engelhart S，Hanfland J，Glasmacher A，et al. Impact of portable air filtration units on exposure of haematology-oncology patients to airborne Aspergillus fumigatus spores under field conditions. J Hosp Infect，2003，54：300-304.
13.	Rivera A，Hohl T，Pamer EG. Immune response to Aspergillus fumigatus infections. Biol Blood Marrow Transplant，2006，12：47-49.
14.	Holgate ST，Lackie P，Wilson S，et al. Bronchial epithelium as a key regulator of airway allergen sensitization and remodeling in asthma. Am J Respir Crit Care Med，2000，162：S113-S117.
15.	Holgate ST. The airway epithelium is central to the pathogenesis of asthma. Allergol Int，2008，57：1-10.
16.	Kauffman HF，Tomee JF，van de Riet MA，et al. Protease-dependent activation of epithelial cells by fungal allergens leads to morphologic changes and cytokine production. J Allergy Clin Immunol，2000，105：1185-1193.
17.	Kohri K，Ueki IF，Shim JJ，et al. Pseudomonas aeruginosa induces MUC5AC production via epidermal growth factor receptor. Eur Respir J，2002，20：1263-1270.
18.	Shao MX，Ueki IF，Nadel JA. Tumor necrosis factor alpha-converting enzyme mediates MUC5AC mucin expression in cultured human airway epithelial cells. Proc Natl Acad Sci USA，2003，100：11618-11623.
19.	Takeyama K，Jung B，Shim JJ，et al. Activation of epidermal growth factor receptors is responsible for mucin synthesis induced by cigarette smoke. Am J Physiol Lung Cell Mol Physiol，2001，280：L165-172.
20.	Takeyama K，Dabbagh K，Jeong Shim J，et al. Oxidative stress causes mucin synthesis via transactivation of epidermal growth factor receptor：role of neutrophils. J Immunol，2000，164：1546-1552.
21.	Shim JJ，Dabbagh K，Ueki IF，et al. IL-13 induces mucin production by stimulating epidermal growth factor receptors and by activating neutrophils. Am J Physiol Lung Cell Mol Physiol，2001，280：L134-140.
22.	Thai P，Loukoianov A，Wachi S，et al. Regulation of airway mucin gene expression. Annu Rev Physiol，2008，70：405-429.
23.	Takeyama K，Tamaoki J，Kondo M，et al. Role of epidermal growth factor receptor in maintaining airway goblet cell hyperplasia in rats sensitized to allergen. Clin Exp Allergy，2008，38：857-865.

1. Burgel PR，Nadel JA. Roles of epidermal growth factor receptor activation in epithelial cell repair and mucin production in airway epithelium. Thorax，2004，59：992-996.
2. Puddicombe SM，Polosa R，Richter A，et al. Involvement of the epidermal growth factor receptor in epithelial repair in asthma. FASEB J，2000，14：1362-1374.
3. Denning DW，O’Driscoll BR，Hogaboam CM，et al. The link between fungi and severe asthma：a summary of the evidence. Eur Respir J，2006，27：615-626.
4. Gao FS，Qiao JO，Zhang Y，Jin XQ. Chronic intranasal administration of Aspergillus fumigatus spores leads to aggravation of airway inflammation and remodeling in asthmatic rats. Respirology，2009，14：360-370.
5. Palmans E，Kips JC，Pauwels RA. Prolonged allergen exposure induces structural airway changes in sensitized rats. Am J Respir Crit Care Med，2000，161：627-635.
6. 高福生，龙飞，祁卉卉，等. 反复吸入烟曲霉孢子对慢性阻塞性肺疾病大鼠气道炎症和重构的影响. 中国呼吸和危重监护杂志，2008，7：205-209.
7. Glaab T，Mitzner W，Braun A，et al. Repetitive measurements of pulmonary mechanics to inhaled cholinergic challenge in spontaneously breathing mice. J Appl Physiol，2004，97：1104-1111.
8. Sumi Y，Foley S，Daigle S，et al. Structural changes and airway remodelling in occupational asthma at a mean interval of 14 years after cessation of exposure. Clin Exp Allergy，2007，37：1781-178.
9. Snibson KJ，Bischof RJ，Slocombe RF，et al. Airway remodelling and inflammation in sheep lungs after chronic airway challenge with house dust mite. Clin Exp Allergy，2005，35：146-152.
10. Leigh R，Ellis R，Wattie J，et al. Dysfunction and remodeling of the mouse airway persist after resolution of acute allergen-induced airway inflammation. Am J Respir Cell Mol Biol，2002，27：526-535.
11. Ou XM，Feng YL，Wen FQ，et al. Macrolides attenuate mucus hypersecretion in rat airways through inactivation of NF-?B. Respirology，2008，13：63-72.
12. Engelhart S，Hanfland J，Glasmacher A，et al. Impact of portable air filtration units on exposure of haematology-oncology patients to airborne Aspergillus fumigatus spores under field conditions. J Hosp Infect，2003，54：300-304.
13. Rivera A，Hohl T，Pamer EG. Immune response to Aspergillus fumigatus infections. Biol Blood Marrow Transplant，2006，12：47-49.
14. Holgate ST，Lackie P，Wilson S，et al. Bronchial epithelium as a key regulator of airway allergen sensitization and remodeling in asthma. Am J Respir Crit Care Med，2000，162：S113-S117.
15. Holgate ST. The airway epithelium is central to the pathogenesis of asthma. Allergol Int，2008，57：1-10.
16. Kauffman HF，Tomee JF，van de Riet MA，et al. Protease-dependent activation of epithelial cells by fungal allergens leads to morphologic changes and cytokine production. J Allergy Clin Immunol，2000，105：1185-1193.
17. Kohri K，Ueki IF，Shim JJ，et al. Pseudomonas aeruginosa induces MUC5AC production via epidermal growth factor receptor. Eur Respir J，2002，20：1263-1270.
18. Shao MX，Ueki IF，Nadel JA. Tumor necrosis factor alpha-converting enzyme mediates MUC5AC mucin expression in cultured human airway epithelial cells. Proc Natl Acad Sci USA，2003，100：11618-11623.
19. Takeyama K，Jung B，Shim JJ，et al. Activation of epidermal growth factor receptors is responsible for mucin synthesis induced by cigarette smoke. Am J Physiol Lung Cell Mol Physiol，2001，280：L165-172.
20. Takeyama K，Dabbagh K，Jeong Shim J，et al. Oxidative stress causes mucin synthesis via transactivation of epidermal growth factor receptor：role of neutrophils. J Immunol，2000，164：1546-1552.
21. Shim JJ，Dabbagh K，Ueki IF，et al. IL-13 induces mucin production by stimulating epidermal growth factor receptors and by activating neutrophils. Am J Physiol Lung Cell Mol Physiol，2001，280：L134-140.
22. Thai P，Loukoianov A，Wachi S，et al. Regulation of airway mucin gene expression. Annu Rev Physiol，2008，70：405-429.
23. Takeyama K，Tamaoki J，Kondo M，et al. Role of epidermal growth factor receptor in maintaining airway goblet cell hyperplasia in rats sensitized to allergen. Clin Exp Allergy，2008，38：857-865.

Chinese Journal of Respiratory and Critical Care Medicine

Effects of Chronic Aspergillus Fumigatus Exposure on Epithelial Cell Injury and Expression of Epidermal Growth Factor Receptor in Airways of Asthmatic Rats

Abstract Full text Figures/Tables Video References Cited by

Format

Content