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C1 inhibitor regulates the activation of the mannose binding lectin‐dependent lectin pathway following ischemia‐reperfusion
Author(s) -
McMullen Meghan E,
Takahashi Minoru,
Davis Alvin,
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.a1145
Subject(s) - lectin pathway , mannan binding lectin , chemistry , complement system , lectin , ficolin , microbiology and biotechnology , pharmacology , immunology , biochemistry , alternative complement pathway , biology , antibody
The mannose binding lectin (MBL)‐dependent lectin complement pathway has been identified as the initiator of complement activation following gastrointestinal ischemia‐reperfusion (GI/R). Mannose associated serine protease‐1/3 deficient mice (MASP‐1/3 KO) were used in a GI/R model to investigate the role of MASP family proteins in GI/R tissue injury. MASP‐1/3 KO mice had higher levels of serum alanine aminotransferase and pulmonary neutrophil infiltration, indicators of secondary liver and lung injury, respectively; compared to WT mice following GI/R. In vitro analysis of serum indicated that MASP‐1/3 KO mice do not have increased MBL A/C concentrations compared to WT mice; however, the MASP‐1/3 KO mice have increased MASP‐2 activity. Reconstitution of MASP‐1/3 KO sera with recombinant MASP‐1 attenuated MASP‐2 activity. These data suggest that MASP‐1/3 negatively regulates MASP‐2 activity. Interestingly, C1 inhibitor was present in MBL complexes of WT mice; however, the amounts of C1 inhibitor present in MBL complexes of MASP‐1/3 KO mice were reduced. Sera from C1 inhibitor deficient mice had even greater levels of MASP‐2 activity when compared to WT or MASP‐1/3 KO mice. Collectively, these data identify a novel regulatory mechanism of MASP‐1/3 in which it modulates the binding of C1 inhibitor to the MBL complex, which regulates MASP‐2 activity. This work was supported by HL52886, HL56086 and HL76130.