Activation of the lectin pathway by natural IgM in a model of ischemia/reperfusion injury.
Reperfusion of ischemic tissues elicits an acute inflammatory response involving serum complement, which is activated by circulating natural IgM specific to self-Ags exposed by ischemia. Recent reports demonstrating a role for the lectin pathway raise a question regarding the initial events in complement activation. To dissect the individual roles of natural IgM and lectin in activation of complement, mice bearing genetic deficiency in early complement, IgM, or mannan-binding lectin were characterized in a mesenteric model of ischemia reperfusion injury. The results reveal that IgM binds initially to ischemic Ag providing a binding site for mannan-binding lectin which subsequently leads to activation of complement and injury.
Zhang
Ming
M
CBR Institute of Biomedical Research Inc., Harvard Medical School, 800 Huntington Avenue, Boston, MA 02115, USA.
Takahashi
Kazue
K
Alicot
Elisabeth M
EM
Vorup-Jensen
Thomas
T
Kessler
Benedikt
B
Thiel
Steffen
S
Jensenius
Jens Christian
JC
Ezekowitz
R Alan B
RA
Moore
Francis D
FD
Carroll
Michael C
MC
D000595:Amino Acid Sequence; D000818:Animals; D000936:Antigen-Antibody Complex; D001324:Autoantigens / Q000235:genetics / Q000276:immunology; D037582:Complement Pathway, Mannose-Binding Lectin / Q000276:immunology*; D004195:Disease Models, Animal; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism*; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D037601:Mannose-Binding Lectin / Q000276:immunology / Q000378:metabolism*; D013058:Mass Spectrometry; D008643:Mesentery / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D018995:Myosin Heavy Chains / Q000235:genetics / Q000276:immunology; D024462:Myosin Type II / Q000235:genetics / Q000276:immunology; D015427:Reperfusion Injury / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D000936:Antigen-Antibody Complex; D001324:Autoantigens; D007075:Immunoglobulin M; D037601:Mannose-Binding Lectin; C483905:Myh14 protein, mouse; D024462:Myosin Type II; D018995:Myosin Heavy Chains