Role of complement in a murine model of peanut-induced anaphylaxis.

Abstract

Peanut allergy is severe and persisting from childhood to adulthood. However, there is no effective prophylaxis or treatment for peanut allergy. Little is known to about the molecular process in the pathogenesis of peanuts allergy, especially in innate immunity. Thus we investigated the role of complement activation in murine peanut anaphylaxis. Complement component C3 deposition on peanut extract (PE) was evaluated using sera from wild-type (WT), mannose-binding lectin associated serine protease (MASP)-1/3 deficient, MASP-2 deficient, and C4 deficient mice. Sera from interferon regulatory factor-4 (IRF-4) deficient mice, which lack serum immunoglobulin, were also used. In anaphylaxis study, mice were pretreated with propranolol and a long-acting form of IL-4, and injected with PE. Mice were then assessed for plasma C3a levels and hypothermia shock by ELISA and rectal temperature measurement, respectively. C3 deposition on PE was abolished in immunoglobulin- and C4-deficient sera. No difference in C3 deposition levels were observed among WT, MASP-1/3 deficient and MASP-2 deficient sera. IgM, IgG2b, IgG3, C1q, and ficolin-A deposits were detected on PE. In anaphylaxis study, MASP-1/3 deficient mice showed elevation of plasma C3a levels similar to WT mice. However, they were significantly reduced in C4- and MASP-2-deficient mice compared to WT mice. Consistently, PE-induced anaphylactic shock was prevented in C4 deficient mice and partially in MASP-2 deficient mice. In conclusion, PE activates complement via both the lectin and classical pathways in vivo, and the complement activation contributes to hypothermia shock in mice.

• Authors: Toshihisa Kodama, Hideharu Sekine, Minoru Takahashi, Daisuke Iwaki, Takeshi Machida, Kazuko Kanno, Yumi Ishida, Yuichi Endo, Teizo Fujita
• Journal: Immunobiology (Immunobiology) Vol. 218 Issue 6 Pg. 844-50 (Jun 2013) ISSN: 1878-3279 [Electronic] Netherlands
• PMID: 23182714 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 Elsevier GmbH. All rights reserved.

Chemical References

• Complement C3
• Complement C4
• Immunoglobulins
• Interferon Regulatory Factors
• Plant Extracts
• interferon regulatory factor-4
• Complement C1q
• Complement System Proteins
• MASP-1 protein, mouse
• MASP-2 protein, mouse
• MASP-3 protein, mouse
• Mannose-Binding Protein-Associated Serine Proteases

Topics

• Animals
• Arachis (immunology)
• Body Temperature (immunology, physiology)
• Cold-Shock Response (immunology)
• Complement Activation (immunology, physiology)
• Complement C1q (immunology, physiology)
• Complement C3 (immunology, physiology)
• Complement C4 (genetics, immunology, physiology)
• Complement System Proteins (immunology, physiology)
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Humans
• Immunoglobulins (blood, genetics, immunology)
• Interferon Regulatory Factors (deficiency, genetics, immunology)
• Mannose-Binding Protein-Associated Serine Proteases (genetics, immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Peanut Hypersensitivity (blood, genetics, immunology)
• Plant Extracts (immunology)