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, Volume 39, Supplement 1, pp C132–C135 | Cite as

Human eosinophil major basic protein augments bronchoconstriction induced by intravenous agonists in guinea pigs

  • S. N. Desai
  • G. Van
  • J. Robson
  • L. G. Letts
  • R. H. Gundel
  • G. J. Gleich
  • P. J. Piper
  • T. C. Noonan
Lung Inflammation

Abstract

The direct effect of intratracheal (IT) administration of human major basic protein (MBP) on pulmonary inspiratory pressure (PIP), and the effect on agonist-induced change in PIP, were determined in anesthetized, ventilated guinea pigs. 500 μg MBP increased PIP from 24.1±4.3 to 49.8±7.4 cm H2O (p<0.002,n=10). Maximum PIP was achieved within 30 min after 500 μg MBP. The direct PIP response to 250 μg MBP was not different from vehicle. The PIP responses to intravenous (IV) acetylcholine (Ach) and 5-hydroxytryptamine (5-HT) were measured before and after administration of 250 μg MBP (n=12). MBP caused a modest, but significant potentiation of the increase in PIP induced by 1, 3 and 10 μg/kg Ach (24, 32 and 28%, respectively,p<0.02) and to 1 μg/kg 5-HT (43%p<0.02). We conclude that MBP at a dose that does not directly affect inspiratory pressure is capable of augmenting the PIP response to IV Ach and 5-HTin vivo.

Keywords

Direct Effect Acetylcholine Basic Protein Inspiratory Pressure Human Eosinophil 

References

  1. [1]
    T. L. Wasmoen, M. P. Bell, D. A. Loegering, G. J. Gleich, F. G. Prendergast and D. J. McKean,Biochemical and amino acid sequence analysis of human eosinophil granule major basic protein. J. Biol. Chem.263, 12559–12563 (1988).PubMedGoogle Scholar
  2. [2]
    E. Frigas, D. A. Loegering and G. J. Gleich,Cytotoxic effects of guinea pig eosinophil major basic protein on tracheal epithelium. Lab. Invest.42, 35–43 (1980).PubMedGoogle Scholar
  3. [3]
    E. Frigas, D. A. Loegering, G. L. Solley, G. M. Farrow and G. J. Gleich,Elevated levels of the eosinophil granule major basic protein in the sputum of patients with bronchial asthma. Mayo Clin. Proc.56, 345–53 (1981).PubMedGoogle Scholar
  4. [4]
    L. A. Laitinen, M. Heino, A. Laitinen, T. Kava and T. Haahtela,Damage of the airway epithelium and bronchial reactivity in patients with asthma. Am. Rev. Respir. Dis.131, 599–606 (1985).PubMedGoogle Scholar
  5. [5]
    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).PubMedGoogle Scholar
  6. [6]
    White, S. R., S. Ohno, J. S. Blake, N. M. Munoz, G. J. Gleich, C. Abrahams, J. Solway and A. R. Leff,Epithelial-dependent contraction of airway smooth muscle caused by eosinophil MBP. Am. J. Physiol.259, L294–303 (1991).Google Scholar
  7. [7]
    Peters, M. S., A. L. Schroeter, G. M. Kephart and G. J. Gleich,Localization of eosinophil granule major basic protein in chronic urticaria. J. Invest. Dermatol.81, 39–43 (1983).CrossRefPubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag 1993

Authors and Affiliations

  • S. N. Desai
    • 1
    • 2
    • 3
  • G. Van
    • 1
    • 2
    • 3
  • J. Robson
    • 1
    • 2
    • 3
  • L. G. Letts
    • 1
    • 2
    • 3
  • R. H. Gundel
    • 1
    • 2
    • 3
  • G. J. Gleich
    • 1
    • 2
    • 3
  • P. J. Piper
    • 1
    • 2
    • 3
  • T. C. Noonan
    • 1
    • 2
    • 3
  1. 1.Department of PharmacologyBoehringer Ingelheim Pharmaceuticals Inc.RidgefieldUSA
  2. 2.Mayo Clinic and FoundationMayo Medical SchoolRochesterUSA
  3. 3.The Royal College of SurgeonsLondonUK

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