Neutrophil elastase cleaves C3bi on opsonized pseudomonas as well as CR1 on neutrophils to create a functionally important opsonin receptor mismatch. Activation of complement components C3 and C5 by a cysteine proteinase (gingipain-1) from Porphyromonas (Bacteroides) gingivalis. Cross-talk between the complement pathway and the contact activation system of coagulation: activated factor XI neutralizes complement factor H. This study provides evidence that complement activation may occur within various cells and may have broad physiological significance. Intracellular complement activation sustains T cell homeostasis and mediates effector differentiation. This study provides biological insights into C3 inhibition in severe COVID-19 and the first clinical proof of concept for extrinsic routes of C3 activation. Complement C3 inhibition in severe COVID-19 using compstatin AMY-101. Aliskiren inhibits renin-mediated complement activation. Molecular intercommunication between the complement and coagulation systems. Kallikrein cleaves C3 and activates complement. Single-molecule kinetics of pore assembly by the membrane attack complex. This review revisits the role of anaphylatoxins and provides a conceptual framework for understanding their broad immunomodulatory functions. Is the complement activation product C3a a proinflammatory molecule? Re-evaluating the evidence and the myth. Complement component C3 - the ‘Swiss army knife’ of innate immunity and host defense. Therapeutic control of complement activation at the level of the central component C3. The role of complement in the mechanism of action of therapeutic anti-cancer mAbs. Structures of C1-IgG1 provide insights into how danger pattern recognition activates complement. This study provided structural insights into the activation of the classical pathway by hexameric antigen–IgG complexes. Complement is activated by IgG hexamers assembled at the cell surface. Manipulating the mediator: modulation of the alternative complement pathway C3 convertase in health, disease and therapy. A journey through the lectin pathway of complement-MBL and beyond. Toward a structure-based comprehension of the lectin pathway of complement. Complement - tapping into new sites and effector systems. Complement system part I - molecular mechanisms of activation and regulation. Complement: a key system for immune surveillance and homeostasis. Ricklin, D., Hajishengallis, G., Yang, K. The complement cascade repurposed in the brain. Proteolytic cascades and their involvement in invertebrate immunity. Complement in disease: a defence system turning offensive. Novel mechanisms and functions of complement. We thus highlight major therapeutic concepts and milestones in clinical complement intervention. The pervasive contribution of complement to disease pathophysiology has inspired a resurgence of complement therapeutics with major clinical developments, some of which have challenged long-held dogmas. Despite its tight spatiotemporal regulation, complement activation can be derailed, fuelling inflammatory tissue pathology. It highlights illustrative paradigm shifts that have reshaped our understanding of complement pathobiology, drawing examples from evolution, development of the central nervous system, tissue regeneration and cancer immunity. This Review provides a guide to the system-wide functions of complement. Besides modulating host–pathogen interactions, this crosstalk guides early developmental processes and distinct cell trajectories, shaping tissue immunometabolic and regenerative programmes in different physiological systems. Complement engages in intricate crosstalk with multiple pattern-recognition and signalling pathways both in the extracellular and intracellular space. Yet, growing evidence has illuminated a broader involvement of complement in fundamental biological processes extending far beyond its traditional realm in innate immunity. Complement has long been considered a key innate immune effector system that mediates host defence and tissue homeostasis.
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