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Early complement factors in the local tissue immunocomplex generated during intestinal ischemia/reperfusion injury

Authors
 Haekyung Lee  ;  Danielle J. Green  ;  Lawrence Lai  ;  Yunfang Joan Hou  ;  Jens C. Jensenius  ;  David Liu  ;  Cheolho Cheong  ;  Chae Gyu Park  ;  Ming Zhang 
Citation
 MOLECULAR IMMUNOLOGY, Vol.47(5) : 972-981, 2010 
Journal Title
 MOLECULAR IMMUNOLOGY 
ISSN
 0161-5890 
Issue Date
2010
MeSH
Animals ; Antigen-Antibody Complex/genetics ; Antigen-Antibody Complex/immunology* ; Autoantigens/genetics ; Autoantigens/immunology ; Autoimmunity/genetics ; Autoimmunity/immunology ; Complement Pathway, Mannose-Binding Lectin/genetics ; Complement Pathway, Mannose-Binding Lectin/immunology ; Complement System Proteins/genetics ; Complement System Proteins/immunology* ; Immunity, Innate/genetics ; Immunity, Innate/immunology ; Immunoglobulin M/genetics ; Immunoglobulin M/immunology* ; Inflammation/genetics ; Inflammation/immunology ; Inflammation/pathology ; Intestines/immunology* ; Intestines/pathology ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Myosin Heavy Chains/genetics ; Myosin Heavy Chains/immunology ; Myosin Type II/genetics ; Myosin Type II/immunology ; Reperfusion Injury/genetics ; Reperfusion Injury/immunology* ; Reperfusion Injury/pathology
Abstract
Recent work reveals that the innate immune system is able to recognize self-targets and initiate an inflammatory response similar to that of pathogens. One novel example of this innate autoimmunity is ischemia/reperfusion (I/R) injury, in which reperfusion of the ischemic tissues elicits an acute inflammatory response activated by natural IgM (nIgM) binding to ischemia-specific self-antigens, which are non-muscle myosin heavy chains type II (NMHC-II) subtype A and C. Subsequently, the complement lectin pathway is activated and eventually tissue injury occurs. Although earlier studies in the intestinal model showed that the classical complement pathway did not initiate I/R injury, C1q deposition was still observed in the local injured tissues by imaging analysis. Moreover, the involvement of the alternative complement pathway became unclear due to conflicting reports using different knockout mice. To explore the immediate downstream pathway following nIgM-ischemic antigen interaction, we isolated the nIgM-ischemic antigen immunocomplexes from the local tissue of animals treated in the intestinal I/R injury model, and examined the presence of initial molecules of three complement pathways. Our results showed that mannan-binding lectin (MBL), the early molecule of the lectin pathway, was present in the nIgM-ischemic Ag immunocomplex. In addition, C1q, the initial molecule of the classical pathway was also detected on the immunocomplex. However, Factor B, the early molecule in the alternative pathway, was not detected in the immunocomplex. To further examine the role of the alternative pathway in I/R injury, we utilized Factor B knockout mice in the intestinal model. Our results showed that Factor B knockout mice were not protected from local tissue injury, and their complement system was activated in the local tissues by nIgM during I/R. These results indicated that the lectin complement pathway operates immediately downstream of the nIgM-ischemic antigen interaction during intestinal I/R. Furthermore, the classical complement pathway also appears to interact with the of nIgM-ischemic antigen immunocomplex. Finally, the alternative complement pathway is not involved in I/R injury induction in the current intestinal model.
Files in This Item:
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DOI
10.1016/j.molimm.2009.11.022
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Park, Chae Gyu(박채규) ORCID logo https://orcid.org/0000-0003-1906-1308
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/103279
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