Auxiliary activation of the complement system and its importance for the pathophysiology of clinical conditions.

Activation and regulation of the cascade systems of the blood (the complement system, the coagulation/contact activation/kallikrein system, and the fibrinolytic system) occurs via activation of zymogen molecules to specific active proteolytic enzymes. Despite the fact that the generated proteases are all present together in the blood, under physiological conditions, the activity of the generated proteases is controlled by endogenous protease inhibitors. Consequently, there is remarkable little crosstalk between the different systems in the fluid phase.

Role of Hemorrhagic Shock in Experimental Polytrauma.

Hemorrhagic shock (HS) after tissue trauma increases the complication and mortality rate of polytrauma (PT) patients. Although several murine trauma models have been introduced, there is a lack of knowledge about the exact impact of an additional HS. We hypothesized that HS significantly contributes to organ injury, which can be reliably monitored by detection of specific organ damage markers.

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.

Complement-coagulation crosstalk on cellular and artificial surfaces.

The humoral serine proteases of the complement system and the coagulation system play central roles during the events of an inflammatory response. While the complement system confers immunoprotective and -regulatory functions, the coagulation cascade is responsible to ensure hemostatic maintenance. Although these two systems individually unfold during inflammation, several studies have reported on the "crosstalk" between components of the complement and the coagulation system in the fluid phase.

Mesenchymal Stem Cells after Polytrauma: Actor and Target.

Mesenchymal stem cells (MSCs) are multipotent cells that are considered indispensable in regeneration processes after tissue trauma. MSCs are recruited to damaged areas via several chemoattractant pathways where they function as "actors" in the healing process by the secretion of manifold pro- and anti-inflammatory, antimicrobial, pro- and anticoagulatory, and trophic/angiogenic factors, but also by proliferation and differentiation into the required cells. On the other hand, MSCs represent "targets" during the pathophysiological conditions after severe trauma, when excessively generated inflammatory mediators, complement activation factors, and damage- and pathogen-associated molecular patterns challenge MSCs and alter their functionality.

Complement therapeutic strategies in trauma, hemorrhagic shock and systemic inflammation - closing Pandora's box?

After severe trauma, the immune system is challenged with a multitude of endogenous and exogenous danger molecules. The recognition of released danger patterns is one of the prime tasks of the innate immune system. In the last two decades, numerous studies have established the complement cascade as a major effector system that detects and processes such danger signals.

Early Detection of Junctional Adhesion Molecule-1 (JAM-1) in the Circulation after Experimental and Clinical Polytrauma.

Severe tissue trauma-induced systemic inflammation is often accompanied by evident or occult blood-organ barrier dysfunctions, frequently leading to multiple organ dysfunction. However, it is unknown whether specific barrier molecules are shed into the circulation early after trauma as potential indicators of an initial barrier dysfunction. The release of the barrier molecule junctional adhesion molecule-1 (JAM-1) was investigated in plasma of C57BL/6 mice 2 h after experimental mono- and polytrauma as well as in polytrauma patients (ISS ≥ 18) during a 10-day period.