Hemorrhagic shock induces renal complement activation
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Complement is activated in hemorrhagic shock and protective effects by specific complement inhibition were shown. However, it remains unclear if complement activation contributes to the local tissue damage and organ failure. Zonulin is known to activate complement and affect organ failure. Therefore, local and systemic complement activation during hemorrhagic shock and its consequences on zonulin were examined.
Porcine hemorrhagic shock (n = 9) was initiated with mean arterial blood pressure maintained constant for 4 h before retransfusion. Before, 4 h after hemorrhage and 12 and 22 h after resuscitation, central and renal blood samples were drawn. Analysis included HMGB-1, C3a, and zonulin (blood and kidney homogenisates) as well as terminal complement complex (TCC) and CH50 (blood). Organ samples were taken for histological and immunohistochemical analyses (C3c).
HMGB-1 was significantly elevated in plasma 4 h after hemorrhagic shock and in homogenized kidneys. TCC after 12 h was significantly elevated centrally, while renal levels were not altered. In contrast, CH50 showed diminished renal values, while normal central levels were observed. Local complement activation was observed with enhanced C3c deposition in kidneys. Zonulin showed significantly diminished levels at 12 and 22 h after hemorrhagic shock (central and renal) and significantly correlated with levels of CH50 and neutrophil gelatinase-associated lipocalin (NGAL).
The more pronounced complement activation centrally might indicate consumption of complement products in kidney tissue, which is underlined by C3c staining. Together with diminished levels of zonulin in both systemic and local samples, results could indicate the involvement of complement as well as zonulin in acute kidney failure.
KeywordsComplement Hemorrhagic shock Tight junction Acute kidney failure Zonulin
This work is supported by grants from the German Research Foundation (DFG) to MH-L and P-R (SFB1149 A01, B03, Z02).
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Conflict of interest
All authors report no conflict of interests.
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