Contribution of Anaphylatoxins to Allergic Inflammation in Human Lungs

Abstract

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.

The Role of Anaphylatoxins C3a and C5a in Regulating Innate and Adaptive Immune Responses

“…murine BM derived DC, human monocyte derived DC) in response to pathogenic or inflammatory stimuli (e.g. LPS, interferons, prostaglandin E 2 ) [11,23,24], and in inflamed lung tissues [22,[32][33][34][35]. These findings imply the roles for C3aR and C5aR in inflammatory and immunological diseases.…”

Increased Inhibitory Capacity of an Anti‐C5a Complementary Peptide Following Acetylation of N‐terminal Alanine

“…These results suggested that AcPepA is more resistant to proteases from neutrophils than PepA. Recently, we demonstrated in preliminary experiments with human lung tissues that AcPepA could interfere with C5a function to enhance cysteinyl-leukotrienes (1).…”

Human colonic epithelial cells detect and respond to C5a via apically expressed C5aR through the ERK pathway

“…Primers for ␤-actin, C4, and CXCL8 (IL-8) have been published earlier (see Table 1). The deoxynucleotide primer sequences for factor B and C5aR were obtained from existing publications (2,46). Primers for C5 and C5L2 were designed from cDNA sequences (reference nos.…”