Role of Complement C5 in Experimental Blunt Chest Trauma-Induced Septic Acute Lung Injury (ALI)

Abstract

BackgroundSevere blunt chest trauma is associated with high mortality. Sepsis represents a serious risk factor for mortality in acute respiratory distress syndrome (ARDS). In septic patients with ARDS complement activation products were found to be elevated in the plasma. In single models like LPS or trauma complement has been studied to some degree, however in clinically highly relevant double hit models such as the one used here little data is available. Here, we hypothesized that absence of C5 is correlated with a decreased inflammatory response in trauma induced septic acute lung injury.Methods12 hrs after DH in mice the local and systemic cytokines and chemokines were quantified by multiplex bead array or ELISA, activated caspase-3 by western blot. Data were analyzed using one-way ANOVA followed by post-hoc Sidak’s multiple comparison test (significance, p≤ 0.05).ResultsIn lung tissue interleukin (IL)-6, monocyte chemo attractant protein-1 (MCP-1) and granulocyte-colony stimulating factor (G-CSF) was elevated in both C5-/- mice and wildtype littermates (wt), whereas caspase-3 was reduced in lungs after DH in C5-/- mice. Systemically, reduced keratinocyte-derived chemokine (KC) levels were observed after DH in C5-/- compared to wt mice. Locally, lung myeloperoxidase (MPO), protein, IL-6, MCP-1 and G-CSF in brochoalveolar lavage fluid (BALF) were elevated after DH in C5-/- compared to wt.ConclusionsIn the complex but clinically relevant DH model the local and systemic inflammatory immune response features both, C5-dependent and C5-independent characteristics. Activation of caspase-3 in lung tissue after DH was C5-dependent whereas local inflammation in lung tissue was C5-independent.

Complement After Trauma: Suturing Innate and Adaptive Immunity

“…Elaborating on the temporal aspect, the treatment with anti-C5a early post-blunt chest trauma in rats ameliorated subsequent leukocytosis, reduced white blood cell recruitment in the lung, and also decreased trauma induced TNF-α levels ( 178 ). As for local effects, 12 h after blunt chest trauma coupled with sepsis induction, C5 deficient mice exhibited decrease in cytokines IL-6 and monocyte chemotactic protein-1 levels in the lung tissue ( 179 ). Local healing processes are actively under the regulation of C5a, as its cognate receptor C5aR1 deficiency (C5aR1-/-) affected fracture healing in a mouse model of femoral fracture ( 180 ).…”

An enlightening role for cytokine storm in coronavirus infection

“…Acute lung injury (ALI) is a common consequence of a cytokine storm and always associated with confirmed or suspected infections in the lung or other organs [ 29 ]. The main characteristic of ALI is inflammatory cell (granulocyte and monocyte) infiltration followed by collagen distribution and deposition [ 64 , 65 ]. Virus-induced lung injury could rapidly progress to ALI or acute respiratory distress syndrome (ARDS), a severe form of ALI, as seen with SARS-CoV and highly pathogenic influenza virus infections [ 66 , 67 ].…”

COVID-19: Lung-Centric Immunothrombosis

“…Time: time of sample collections in hours after insult. Study 1 (Kalbitz et al, 2016): mice were subjected to a double-hit (DH)insult consisting of bilateral lung contusion followed 24 hrs later by cecal ligation and perforation. Indices of lung injury: protein in BALF, MPO activity in lung homogenates.…”