Figure 3.

The complementome role and therapeutic targets in ALI/ARDS. Acute insults can induce exaggerated ComC activation locally and systemically. Complement proteins are produced and released intrahepatically providing the systemic extracellular ComC. Complement proteins are also synthesized extrahepatically (locally) by other cells and the intracellular local ComC plays a pivotal role in cell homeostasis and metabolisms. The activated complementome acts as a pivotal nexus to activate other systems of the immunome, coagulatome, metabolome, and microbiome via that results in air-blood barrier failure, inflammatory pulmonary edema, SIRS, immunothrombosis, meta-inflammation, PICS, and dysbiosis, ultimately leading to the development of ARDS/ALI. ALI, acute lung injury; AP, alternative pathway; AP1, activator protein 1; ARDS, acute respiratory distress syndrome; C3aR, C3a receptor; C5aR, C5a receptor; CP, classical pathway; ECMO, extracorporeal membrane oxygenation; EP, extrinsic pathway; HIF-1α, hypoxia-induced factor 1-alpha; GLUT1, glucose transporter 1; HKI/II, hexokinase I/II; I/R, ischemia/reperfusion, LAF-1, leukocyte adhesion molecule 1; LP, lectin pathway; NETosis, neutrophil extracellular trap formation; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; OXPHOS, oxidative phosphorylation; PICS, persistent inflammation/immunosuppression and catabolism syndrome; ROS, reactive oxidation species; SIRS, systemic inflammatory response syndrome.