Fig. 7.

Schematic representation of the inhibitory effect of the Rho-inhibiting C2IN-C3lim fusion toxin on the chemotactic recruitment of monocytic cells from the blood into the alveolar space after blunt chest trauma (TXT). After blunt chest trauma (thorax trauma), the blood–air barrier between the capillary blood and the alveolar space is partially damaged and neutrophils as well as monocytes are recruited into the alveolar space by chemotaxis. There, these cells release cytokines, which contribute to the local and systemic inflammation and might worsen the outcome of multi-trauma patients. According to the current model, the intratracheally (i.t.) applied Rho-inhibitor C2IN-C3lim (indicated as “C3”) enters the cytosol of monocytes, most likely via receptor-mediated endocytosis and subsequent translocation from endosomes into the cytosol. In the cytosol of monocytes, the C3-catalyzed Rho-ADP-ribosylation inhibits Rho-mediated signal transduction, which interferes with F-actin structure and dynamics thereby inhibiting the chemotactic recruitment of monocytes into the alveolar space