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Investigations on the Involvement of the Lectin Pathway of Complement Activation in Anaphylaxis

Windbichler M.a · Echtenacher B.a · Takahashi K.c · Ezekowitz R.A.B.c · Schwaeble W.J.b · Jenseniuis J.C.d · Männel D.N.a
aInstitute of Immunology, University of Regensburg, Regensburg, Germany; bDepartment of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK; cDepartment of Pediatrics, Laboratory of Developmental Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, Mass., USA; dDepartment of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark Int Arch Allergy Immunol 2006;141:11–23 (DOI:10.1159/000094177)

Abstract

Background: Systemic anaphylaxis is the most severe form of immediate hypersensitivity reaction. The activation of the complement system occurs during anaphylactic shock. The purpose of this study was to determine in a mouse model whether the lectin pathway of complement activation is involved in anaphylaxis. Methods: To see whether the lectin pathway is involved in anaphylactic shock, serum mannan-binding lectin (MBL) levels were measured after passive anaphylaxis. Also MBL expression and binding to potential ligands were investigated. To determine whether complement or mast cell activation is essential for hypothermia in anaphylactic shock, mouse strains deficient in MBL-A and MBL-C, C1q, factors B and C2, C5, C5aR, or mast cells were tested. Results: After antigenic challenge a marked drop in body temperature as well as a rapid decrease in serum MBL levels were observed. The decrease of serum MBL levels in shock could not be attributed to MBL binding to immune complexes or tissues, but an interaction of MBL with mast cell-derived proteoglycans was seen. In contrast to mast cell-deficient mice, none of the complement-deficient mouse strains were protected from shock-associated hypothermia. Conclusions: These results indicate that neither MBL nor activation of the complement cascade is crucial for the induction of anaphylaxis. In contrast mast cell activation is associated with the development of hypothermia and possibly the observed decrease in serum MBL levels.

 

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