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Mannose binding lectin binds IgM to activate the lectin complement pathway in vitro and in vivo
Author(s) -
McMullen Meghan E,
Hart Melanie L.,
Walsh Mary C.,
Buras Jon,
Takahashi Kazue,
Stahl Gregory
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1144-b
Subject(s) - lectin pathway , complement system , mannan binding lectin , lectin , alternative complement pathway , classical complement pathway , hemolysis , in vivo , immunology , immunoglobulin m , in vitro , chemistry , c type lectin , ficolin , complement factor b , biology , microbiology and biotechnology , antibody , immunoglobulin g , biochemistry
Recent evidence has implicated a role for the MBL‐dependent lectin pathway in gastrointestinal ischemia/reperfusion (I/R)‐induced injury. However, previous studies have implicated IgM and the classical pathway as initiators of complement activation following I/R. Thus, we investigated the potential interaction between MBL and IgM leading to complement activation. Using surface plasmon resonance, we demonstrate that MBL does bind human IgM. Subsequently, complement activation was demonstrated following sensitization of human RBCs with anti‐human CD59 IgM. Serum from C1q KO mice, which contains MBL, increased hemolysis compared to serum from MBL‐A/C KO mice, which contains C1q, but not MBL. Treatment of human endothelial cells with anti‐human CD59 IgM, MBL and MASP‐2 deposited C4. These data suggest that the presence of both IgM and MBL can activate the lectin pathway. Serum ALT levels increased in sIgM/MBL‐A/C KO mice reconstituted with WT plasma compared to sIgM/MBL‐A/C KO mice reconstituted with MBL‐A/C KO plasma following gastrointestinal (G) I/R. Similarly, intestinal C3 deposition was greater in sIgM/MBL‐A/C KO mice reconstituted with WT plasma compared to sIgM/MBL‐A/C KO mice treated with MBL‐A/C KO plasma. These data indicate for the first time that both IgM and MBL are required for GI/R‐induced complement activation and subsequent injury. This work was supported by HL52886, HL56086, HL76130.