Abstract
Eosinophil Major Basic Protein (MBP) may be a potent effector in damaging airway epithelium and inducing acute (2–3 h) hyperresponsiveness to agonists in primates. Accordingly, interactions between human eosinophil MBP and guinea-pig airway epithelium were quantitated biochemically. MBP was extracted from human eosinophils and purified by size-exclusion HPLC. This resulted in a single protein band on electrophoresis, which cross-reacted with antisera raised to peptides derived from the predicted sequence of human MBP. This human MBP caused modest, but statistically significant, damage to respiratory epithelium (16.4% increase in efflux of51Cr from guinea-pig tracheal rings) after 3 h of incubation with 10−4 M concentration, but not with lower concentrations. These data demonstrates that MBP cytotoxicity to intact epithelium can be rapidly measuredin vitro, and suggests that rodent airway epithelium may be relatively resistant to the cytotoxic effects of MBP.
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References
S. R. Durham and A. B. Kay,Eosinophils, bronchial hyperreactivity and late-phase asthmatic reactions. Clin. Allergy15, 411–418 (1985).
A. C. Ferguson and F. W. Wong,Bronchial hyperresponsiveness in asthmatic children: correlation with macrophages and eosinophils in broncholavage fluid. Chest96 988–991 (1989).
J. Bousquet, P. Chanez, J. Y. Lacoste, G. Barneon, N. Ghavanian, I. Enander, P. Venge P. S. Ahlstedt, J. Simony-Lafontaine, P. Godard and F. B. Michel,Eosinophilic inflammation in asthma. New Engl. J. Med.323, 1033–1039 (1990).
P. K. Jeffery, A. J. Wardlaw, F. C. Nelson, J. V. Collins and A. B. Kay,Bronchial biopsies in asthma: An ultrastructural, quantitative study and correlation with hypereactivity. Am. Rev. Respir. Dis.140, 1745–1753 (1989).
J. G. R. De Monchy, K. K. Kauffman, P. Venge, G. H. Koeter, H. M. Jansen, H. J. Sluiter and K. De VriesBronchoalvelar eosinophilia during allergen-induced late asthmatic reactions. Am. Rev. Respir. Dis.131, 373–376 (1985).
R. Beasley, W. R. Roche, J. A. Roberts and S. T. Holgate,Cellular events in the bronchi in mild asthma and after bronchial provocation. Am. Rev. Respir. Dis.139, 806–817 (1989).
P. Diaz, M. C. Gonzalez, F. R. Galleguillos, P. Ancic, O. Cromwell, D. Sheperd, S. R. Durham, G. J. Gleich and A. B. Kay,Leukocytes and mediators in bronchoalveolar lavage during allergen-induced late-phase asthmatic reactions. Am. Rev. Respir. Dis.139, 1383–1389 (1989).
E. Frigas and G. J. Gleich,The eosinophil and the pathophysiology of asthma. J. Allergy Clin. Immunol.77, 527–537 (1986).
E. Frigas, D. A. Loegering and G. J. Gleich,Cytotoxic effects of the guinea pig eosinophil major basic protein on tracheal epithelium. Lab. Invest.42, 35–43 (1980).
R. Barker, G. J. Gleich and L. R. Rease,Acidic precursor revealed in human eosinophil granule major basic protein cDNA. J. Exp. Med.168, 1493–1498 (1988).
S. Motojima, E. Frigas, D. A. Loegering and G. J. Gleich.Toxicity of eosinophil cationic proteins for guinea-pig tracheal epithelium in vitro. Am. Rev. Respir. Dis.139, 801–805 (1989).
C-M. Liu and M. Okuda,Injurious effect of eosinophil extract on the human nasal mucosa. Rhinology26, 121–132 (1988).
H. H. Ayars, L. C. Altman, M. M. McManus, J. M. Agosti, L. Baker, D. L. Luchtel, D. A. Loegering and G. J. Gleich,Injurious effect of the eosinophil peroxide-hydrogen peroxide halide system and Major Basic Protein on human nasal epithelium in vitro. Am. Rev. Respir. Dis.140, 125 131 (1989).
R. H. Gundel, L. G. Letts and G. J. Gleich,Human eosinophil Major Basic Protein induces airway constriction and airway hyperresponsiveness in primates. J. Clin. Invest.87, 1470–1473 (1991).
E. Boichot, V. Lagente, C. Carre, P. Waltmann, J. M. Mencia-Huerta and P. Braquet,Bronchial hyperresponsiveness and cellular infiltration in the lung of the guineapigs sensitised and challenged by aerosol. Clin. Exp. Allergy21, 67–76 (1991).
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Tagari, P., Chee, P., Chan, C. et al. Quantitation of eosinophil Major Basic Protein cytotoxicity to rodent respiratory epithelium. Agents and Actions 37, 171–173 (1992). https://doi.org/10.1007/BF02028100
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DOI: https://doi.org/10.1007/BF02028100