Complement C5a Functions as a Master Switch for the pH Balance in Neutrophils Exerting Fundamental Immunometabolic Effects.

During sepsis, excessive activation of the complement system with generation of the anaphylatoxin C5a results in profound disturbances in crucial neutrophil functions. Moreover, because neutrophil activity is highly dependent on intracellular pH (pH), we propose a direct mechanistic link between complement activation and neutrophil pH In this article, we demonstrate that in vitro exposure of human neutrophils to C5a significantly increased pH by selective activation of the sodium/hydrogen exchanger. Upstream signaling of C5a-mediated intracellular alkalinization was dependent on C5aR1, intracellular calcium, protein kinase C, and calmodulin, and downstream signaling regulated the release of antibacterial myeloperoxidase and lactoferrin.

Phagocytosis and digestion of pH-sensitive fluorescent dye (Eos-FP) transfected E. coli in whole blood assays from patients with severe sepsis and septic shock.

The function of phagocytic and antigen presenting cells is of crucial importance to sustain immune competence against infectious agents as well as malignancies. We here describe a reproducible procedure for the quantification of phagocytosis by leukocytes in whole blood. For this, a pH-sensitive green-fluorescent protein- (GFP) like dye (Eos-FP) is transfected into infectious microroganisms.

Autophagy and ATP-induced anti-apoptosis in antigen presenting cells (APC) follows the cytokine storm in patients after major trauma.

Severe trauma and the systemic inflammatory response syndrome (SIRS) occur as a result of a cytokine storm which is in part due to ATP released from damaged tissue. This pathology also leads to increased numbers of immature antigen presenting cells (APC) sharing properties of dendritic cells (DC) or macrophages (MΦ). The occurrence of immature APC appears to coincide with the reactivation of herpes virus infections such as Epstein Barr virus (EBV).