Contribution of anaphylatoxins to allergic inflammation in human lungs.
The contribution of complement activation to allergic asthma remains controversial. In order to elucidate the role played by the complement split products, anaphylatoxins C3a and C5a, we evaluated their effects on production of cysteinyl-leukotrienes (cysLTs) by human lung fragments following an anaphylactic reaction. The lung tissues obtained from two patients with lung cancer showed C5aR-, C5L2R-, and C3aR-mRNA expression. When the chopped lung fragments passively sensitized with human IgE were incubated with anti-human IgE antibody, a significant amount of cysLTs was generated in comparison with the control (without anti-IgE antibody). The co-addition of human C5a at doses of 0.1 to 10 ng/ml to the anti-IgE antibody potentiated cysLT production. The response was bell-shaped in distribution, significant, and peaked at a C5a concentration of 1 ng/ml. The co-addition of human C3a up to 1,000 ng/ml seemed to increase cysLT production, but not to any significant extent. A novel C5a receptor complementary peptide, acetylated peptide A, dose-dependently inhibited cysLT production by the human lung fragments following the anaphylactic reaction in the presence of 1 ng/ml C5a. However, this peptide did not inhibit cysLT production in the presence of 100 ng/ml C3a. It is suggested that the anaphylatoxin C5a potentiates cysLT production in human lung tissues and contributes to allergic inflammation in disorders such as asthma, thus acetylated peptide A may be useful for suppressing allergic inflammation in the lungs.
Abe
Masayoshi
M
Department of Pharmacology, School of Medicine, Fukuoka University, Fukuoka, Japan. abemasa@fukuoka-u.ac.jp
Hama
Hiroshi
H
Shirakusa
Takayuki
T
Iwasaki
Akinori
A
Ono
Nobuhumi
N
Kimura
Nobuhiro
N
Hugli
Tony E
TE
Okada
Noriko
N
Katsuragi
Takeshi
T
Okada
Hidechika
H
D000706:Anaphylatoxins / Q000276:immunology / Q000502:physiology*; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001249:Asthma / Q000276:immunology / Q000378:metabolism; D015926:Complement C3a / Q000494:pharmacology / Q000502:physiology*; D015936:Complement C5a / Q000494:pharmacology / Q000502:physiology*; D003545:Cysteine / Q000378:metabolism*; D006801:Humans; D007073:Immunoglobulin E / Q000494:pharmacology*; D066298:In Vitro Techniques; D015289:Leukotrienes / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D011014:Pneumonia / Q000276:immunology*
D000706:Anaphylatoxins; D000888:Antibodies, Anti-Idiotypic; D015289:Leukotrienes; D010455:Peptides; C510273:acetylated peptide A; C112381:cysteinyl-leukotriene; D007073:Immunoglobulin E; D015926:Complement C3a; D015936:Complement C5a; D003545:Cysteine