Journal of leukocyte biology
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In this mini review, we describe the molecular mechanisms in polymicrobial sepsis that lead to a series of adverse events including activation of inflammatory and prothrombotic pathways, a faulty innate immune system, and multiorgan dysfunction. Complement activation is a well-established feature of sepsis, especially involving generation of C5a and C5b-9, along with engagement of relevant receptors for C5a. Activation of neutrophils by C5a leads to extrusion of DNA, forming neutrophil extracellular traps that contain myeloperoxidase and oxidases, along with extracellular histones. ⋯ The reductions in these three key proteins are complement- and histone-dependent. Dysfunction of these ATPases is linked to the cardiomyopathy of sepsis. These data suggest novel targets in the setting of sepsis in humans.