Fluid resuscitation with hemoglobin vesicles prevents Escherichia coli growth via complement activation in a hemorrhagic shock rat model

Hemoglobin vesicles (HbVs) could serve as a substitute for red blood cells (RBCs) in resuscitation from massive hemorrhage. A massive transfusion of RBCs can increase the risk of infection, which is not caused by contaminating micro-organisms in the transfused RBCs but by a breakdown of the host defense system. We previously found that complement activity was increased after resuscitation with HbVs at a putative dose in a rat model of hemorrhagic shock. It is known that complement system plays a key role in host defense in the embryonic stage. Therefore, the objective of this study was to address whether the suppression of bacterial infections in hemorrhagic shock rats was a result of increased complement activity after massive HbV transfusion. For this purpose, Escherichia coli were incubated with plasma samples obtained from a rat model of hemorrhagic shock resuscitated by HbVs or RBCs, and bacterial growth was determined under ex vivo conditions. As a result, E. coli growth was found to be suppressed by increased complement activity, mediated by the production of IgM from spleen. However, this antibacterial activity disappeared when the E. coli were treated with complement-inactivated plasma obtained from splenoctomized rats. In addition, the resuscitation of HbVs from hemorrhagic shock increased the survival rate and viable bacterial counts in blood in cecum ligation and puncture rats, a sepsis model. In conclusion, the resuscitation of HbVs in the rat model of hemorrhagic shock suppresses bacterial growth via complement activation induced by IgM.