[Study for an allergic inflammation model using human lungs and its pharmacological application].

Abstract

The complement system, which plays an important role in inmate immunity, is considered to be important in the pathophysiology of allergic asthma. A patient with allergic asthma shows the reversible characteristic system of bronchoconstriction, increased mucus secretion, and complicated airway inflammation. Various cytokines secreted from Th2 cells contribute to the system. Cysteinyl-leukotrienes (CysLTs) are also considered to be one of the important mediators involved in asthmatic pathophysiology. However, the effects of a drug on humans may not be the same as those on animals due to species differences in complement-related molecules. In this series of experiments, we tried to establish a model in which the effects of a drug on the production of CysLTs from human lung preparations were evaluated following an anaphylactic reaction. CysLT production increased when the passively sensitized lung tissues were stimulated with anti-IgE antibody. The coaddition of anaphylatoxin, C5a, with the anti-IgE antibody potentiated CysLT production. The response to C3a was weaker when compared with that to C5a. In addition, increased production of CysLTs by adding serum at a specific ratio was dose dependently inhibited by nonpeptide C5a receptor antagonist, W-54011, or a novel complementary peptide inhibitor of C5a, acetyl peptide A. From these results, it is suggested that C5a potentiates cysLT production from human lung tissues and contributes to allergic inflammation like asthma, and thus acetylated peptide A and W-54011 are useful for suppressing allergic inflammation in the lungs.

• Authors: Hiroshi Hama, Nobufumi Ono, Masayoshi Abe
• Journal: Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan (Yakugaku Zasshi) Vol. 127 Issue 4 Pg. 721-7 (Apr 2007) ISSN: 0031-6903 [Print] Japan
• PMID: 17409703 (Publication Type: English Abstract, Journal Article, Review)

Chemical References

• Anaphylatoxins
• Aniline Compounds
• Leukotrienes
• N-((4-dimethylaminophenyl)methyl)-N-(4-isopropylphenyl)-7-methoxy-1,2,3,4-tetrahydronaphthalen-1-carboxamide
• Peptide Fragments
• Receptor, Anaphylatoxin C5a
• Tetrahydronaphthalenes
• cysteinyl-leukotriene
• peptide A
• Immunoglobulin E
• Complement C5a
• Oncogene Protein pp60(v-src)
• Cysteine

Topics

• Anaphylatoxins (immunology)
• Aniline Compounds (therapeutic use)
• Asthma (drug therapy, etiology)
• Complement C5a (antagonists & inhibitors, physiology)
• Cysteine (biosynthesis)
• Humans
• Hypersensitivity (drug therapy, etiology)
• Immunoglobulin E (immunology)
• In Vitro Techniques
• Leukotrienes (biosynthesis)
• Lung (metabolism)
• Models, Biological
• Oncogene Protein pp60(v-src) (therapeutic use)
• Peptide Fragments (therapeutic use)
• Receptor, Anaphylatoxin C5a (antagonists & inhibitors)
• Tetrahydronaphthalenes (therapeutic use)