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

Area of Science:

• Immunology
• Complement System Biology
• Pathophysiology of I/R Injury

Background:

• The innate immune system can target self-antigens, leading to inflammation akin to pathogen responses.
• Ischemia/reperfusion (I/R) injury involves natural IgM (nIgM) binding to ischemia-specific self-antigens (NMHC-II A and C), activating complement and causing tissue damage.
• The precise complement pathways involved in I/R injury initiation, particularly the lectin and alternative pathways, remain incompletely understood.

Purpose of the Study:

• To elucidate the immediate downstream complement pathway activation following nIgM-ischemic self-antigen interaction in intestinal I/R injury.
• To investigate the role of the lectin, classical, and alternative complement pathways in the pathogenesis of intestinal I/R injury.

Main Methods:

• Isolation of nIgM-ischemic self-antigen immunocomplexes from the intestinal tissue of an I/R injury model.
• Detection of complement pathway components (MBL, C1q, Factor B) within these immunocomplexes.
• Assessment of I/R injury in Factor B knockout mice to evaluate the alternative pathway's contribution.

Main Results:

• Mannan-binding lectin (MBL) and C1q were detected in nIgM-ischemic self-antigen immunocomplexes, indicating lectin and classical pathway involvement.
• Factor B was not detected in the immunocomplexes, suggesting the alternative pathway is not immediately engaged.
• Factor B knockout mice exhibited no protection from I/R injury, confirming the alternative pathway's non-involvement in this model.

Conclusions:

• The lectin complement pathway is the primary immediate downstream effector following nIgM-ischemic self-antigen binding in intestinal I/R injury.
• The classical complement pathway also appears to interact with the nIgM-ischemic self-antigen complex.
• The alternative complement pathway does not play a significant role in the induction of intestinal I/R injury in this experimental model.