Effects of Polymerized Basic Amino Acids Under 50mer Range of Degree of Polymerization on Physiological and Stimulated Mucin Release from Cultured Hamster Tracheal Surface Epithelial Cells

중합도 50mer 이하의 염기성 아미노산 중합체들이 일차배양 햄스터 기관표면 상피세포에서의 생리적 뮤신유리 및 분비자극 상태에서의 뮤신유리에 미치는 영향

  • 이충재 (충남대학교 의과대학 약리학 교실) ;
  • 이재흔 (충남대학교 의과대학 약리학 교실) ;
  • 석정호 (충남대학교 의과대학 약리학 교실) ;
  • 허강민 (충남대학교 의과대학 약리학 교실)
  • Published : 2002.09.01


In the present study, we tried to investigate whether polymerized basic amino acid e.g. poly-L-lysine (PLL) which has the degree of polymerization under 50mer significantly affects the physiological and stimulated mucin release from cultured hamster tracheal surface epithelial cells. Confluent primary hamster tracheal surface epithelial (HTSE) cells were metabolically radiolabeled with $^3{H}$-glucosamine for 24 hr and chased for 30 min in the presence of either PLLs or adenosine triphosphate (ATP) and PLL to assess the effects on basic or ATP-stimulated $^3{H}$-mucin release. Possible cytotoxicities of PLLs were assessed by measuring lactate dehydrogenase (LDH) release from HTSE cel1s during treatment. The results were as follows: PLLs significantly inhibited basic mucin release from cultured HTSE cells in a dose-dependent manner from the range of 46mer to 14mer; PLL 46mer significantly inhibited the stimulated mucin release by ATP from cultured HTSE cells; there was no significant release of LDH from cultured HTSE cells during treatment. We conclude that PLLs inhibit both physiological and stimulated mucin release from airway epithelial cells without significant cytotoxicity and PLL lost its activity under the range of 14mer. This finding suggests that polymer of basic amino acid like PLL might function as a regulator for hypersecretion of mucus manifested in various respiratory diseases.



  1. Coyle, A.J., Ackerman, S.J. and Irvin, C.G. (1993). Cationic proteins induce airway hyperresponsiveness dependent on charge interactions. Am. Rev. Respir. Dis., 147, 896-900 https://doi.org/10.1164/ajrccm/147.4.896
  2. Elferink, J.G.R. (1991). Changes of plasma membrane perme- ability in neutrophils treated with polycations. Inflamma- tion, 15 (2), 103-115 https://doi.org/10.1007/BF00917505
  3. Frigas, E., Loegering, D.A. and Gleich, G.J. (1980). Cytotoxic effects of the guinea pig eosinophil major basic protein on tracheal epithelium. Lab. Invest., 42, 35-43
  4. Frigas, E., Loegering, D.A., Solley, G.O., Farrow, G.M. and Gleich, G.J. (1981). Elevated levels of the eosinophil granule major basic protein in the sputum of patients with bronchial asthma. Mayo Clin. Proc., 56, 345-353
  5. Gleich, G.J., Flavahan, N.A., Fugisawa, T. and Vanhoutte, P.M. (1988). The eosinophil as a mediator of damage to respiratory epithelium ; a model for bronchial hyperreacti- vity. J. Allergy Clin. Immunol., 81, 776-781 https://doi.org/10.1016/0091-6749(88)90931-1
  6. Gleich, G.J. (1990). The eosinophil and bronchial asthma: Current understanding. J. Allergy Clin. Immunol., 85, 422- 436 https://doi.org/10.1016/0091-6749(90)90151-S
  7. Hammes, M. and Singh, A. (1994). Effect of polycations on permeability of glomerular epithelial cell monolayer to albumin. J. Lab. Clin. Med., 123, 437-446
  8. Kim, K.C., Opaskar-Hincman, H. and Bhaskar, K.R. (1989). Secretions from primary hamster tracheal surface epithelial cells in culture: Mucin-like glycoproteins, Proteoglycans, and lipids. Exp. Lung Res., 15, 299-314 https://doi.org/10.3109/01902148909087860
  9. Kim, K.C., Rearick, J.I., Nettesheim, P. and Jetten, A.M. (1985). Biochemical characterization of mucous glycopro- teins synthesized and secreted by hamster tracheal epithelial cells in primary culture. J. Biol. Chem., 260, 4021-4027
  10. Ko, K.H. (1995). Inhibitor for secretion of mucin. The patent in the Republic of Korea, Registcred No. 6828
  11. Ko, K.H., Lee, C.J., Shin, C.Y., Jo, M.-J. and Kim, K.C. (1999). Inhibition of mucin release from airway goblet cells by polycationic peptides. Am. J. Physiol., 277 (21), L811-L815
  12. Lee, C.J. (2001a). Effects of poly-L-arginine on the mucin release from airway goblet cells of hamster and on the mucosubstances of airway goblet cells of rats. J. Appl. Pharmacol., 9 (4), 263-269
  13. Lee, C.J. (2001b). Specificity in the inhibition of mucin release from airway goblet cells by polycationic peptides. J. Appl. Pharmacol., 9 (3), 218-223
  14. Motogima, S., Frigas, E., Loegering, D.A. and Gleich, G.J. (1989). Toxicity of eosinophil cationic proteins for gunea pig tracheal epithelium in vitro. Am. Rev. Respir. Dis., 139, 801-805 https://doi.org/10.1164/ajrccm/139.3.801
  15. Mutschler, E. and Derendorf, H. (1995). Drug actions. CRC press, Inc., Boca Raton, Florida, 410-411
  16. Newshound, M.T. and Biennenstock, J. (1983). Respiratory tract defense mechanism, In, textbook of pulmonary disease (Baum, G.L. and Wolinsky, E. (eds)), 3rd ed., Little Brown and Company
  17. Pon, D.J., Van Staden, C.J., Boulet, L. and Rodger, l.W. (1994) Hyperplastic effects of aerosolized sodium metasul fite on rat airway mucus-secretory epithelial cells. Can. J. Physiol. Pharmacol., 72, 1025-1030 https://doi.org/10.1139/y94-143
  18. Uchida, D.A- Ackerman, S.J., Coyle, A.J., Larsen, G.L., Weller, P.F., Freed, J. and Irvin, C.G. (1993). The effect of human eosinophil granule major basic protein on airway responsiveness in the rat in vivo. Am. Rev. Respir. Dis., 147, 982-988 https://doi.org/10.1164/ajrccm/147.4.982
  19. Wardaw, A.J., Dunnettc, S., Gleich, G.J., Collins, J.V. and Kay, A.B. (1988) Eosinophils and mast cells in bronchoal- veolar lavage in sujects with mild asthma: relationship to bronchial hyperreactivity. Am. Rev. Respir. Dis., 137, 62-69 https://doi.org/10.1164/ajrccm/137.1.62