The study investigates the role of circulating mitochondrial damage-associated molecular patterns (DAMPs) in the systemic inflammatory response syndrome (SIRS) following injury. Mitochondria, which evolved from bacteria, release formyl peptides and mitochondrial DNA (mtDNA) into the circulation after cellular disruption. These DAMPs activate human neutrophils (PMNs) through formyl peptide receptors (FPRs) and Toll-like receptors (TLRs), leading to PMN Ca²⁺ flux, MAP kinase phosphorylation, and migration. In vitro and in vivo experiments show that MTD can elicit neutrophil-mediated organ injury, particularly in the lung. The study concludes that the release of mitochondrial DAMPs by cellular injury is a key link between trauma, inflammation, and SIRS, providing a novel explanation for the similarity between traumatic and infectious SIRS.The study investigates the role of circulating mitochondrial damage-associated molecular patterns (DAMPs) in the systemic inflammatory response syndrome (SIRS) following injury. Mitochondria, which evolved from bacteria, release formyl peptides and mitochondrial DNA (mtDNA) into the circulation after cellular disruption. These DAMPs activate human neutrophils (PMNs) through formyl peptide receptors (FPRs) and Toll-like receptors (TLRs), leading to PMN Ca²⁺ flux, MAP kinase phosphorylation, and migration. In vitro and in vivo experiments show that MTD can elicit neutrophil-mediated organ injury, particularly in the lung. The study concludes that the release of mitochondrial DAMPs by cellular injury is a key link between trauma, inflammation, and SIRS, providing a novel explanation for the similarity between traumatic and infectious SIRS.