Generation of C5a in the absence of C3: a new complement activation pathway

By M. Huber-Lang, J. Sarma, F. Zetoune, D. Rittirsch, T. Neff, Stephanie R. McGuire, John D Lambris, R. Warner, M. Flierl, L. Hoesel and 5 more. Nature Medicine, 2006

1,027 citations recorded by the source corpus.

Subfields: Genetics, Hematology, Immunology

View Paper: https://www.semanticscholar.org/paper/098a5a8e7e79df67c3765daf9abada159604d8cd

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In Immunology

Citations in the corpus

Locally produced complement fragments C5a and C3a provide both costimulatory and survival signals to naive CD4+ T cells. (2008, result): “These experimental results in conjunction with the recent description of C3 bypass pathways for C5 cleavage (Huber-Lang et al., 2006; Kang et al., 2006) explain why T cell immunity is diminished but not as fully abrogated in the absence of C3, C5, C3aR, or C5aR individually.”
The Complement System (2010, background): “Thrombin, a member of the coagulation pathway, can locally generate C5a in in vivo in C3deficient mice which are unable to generate the conventional C5 convertase (Huber-Lang et al. 2006).”
The role of complement in inflammatory diseases from behind the scenes into the spotlight. (2007, background): “Recent work has shown that C5a can be generated in mice lacking C3 through the proteolytic cleavage of C5 by thrombin.(15) These cleavage reactions result in the generation of active complement components that have proinflammatory properties such as anaphylatoxins as well as C3b or C5b.”
Molecular Intercommunication between the Complement and Coagulation Systems (2010, background): “Surprisingly, the presence of C5a was recently discovered in activated C3deficient serum, where enhanced levels of thrombin, a primary component of the activated coagulation system, induced C5 conversion to C5a (6).”
Complement System Part I – Molecular Mechanisms of Activation and Regulation (2015, background): “Accumulating evidence suggests the existence of additional complement activation pathways in the plasma (217) aside from the three established pathways.”
Complement regulators and inhibitory proteins (2009, background): “Complement is also activated by an additional bypass pathway that acts independently of C3 or bypasses the C3 convertase and is mediated by thrombin acting on the C5 convertas”
Complement and coagulation: strangers or partners in crime? (2007, background): “Recently, the activation of C5 by thrombin [ 44 ] (Figure 1) was demonstrated in C3 knockout mice, in which C5 convertases cannot be formed.”
The coagulopathy of trauma: a review of mechanisms. (2008, background): “Activation of coagulation proteases can induce inflammation through transmembrane protease receptors on cell surfaces(73) and direct activation of complement.(74,75) Degranulating platelets also release lysophospholipid mediators that potentiate immune responses by activation of neutrophils and endo”
TNF and increased intracellular iron alter macrophage polarization to a detrimental M1 phenotype in the injured spinal cord. (2014, neutral): “…IL-18 13 M1 cytokine 0.04 (Bellora et al., 2010) Ltb Lymphotoxin b 7 TNFsf, NFkB inducer 0.03 (Mackay et al., 1998) Hc C5 6 proinflammatory 0.02 (Huber-Lang et al., 2006) B2m b 2 microglobulin 6 Upregulated inM1 cells 0.01 (Corna et al., 2010) Il17f IL17F 5 Inducible by LPS 0.01 (Bosmann et…”
The Role of the Anaphylatoxins in Health and Disease (2009, positive): “…C5a can be generated from C5 by cell-derived proteases (Huber-Lang et al., 2002a), serine proteases of the clotting and the fibrinolysis system (Huber-Lang et al., 2006;Markiewski and Lambris, 2007) and several pathogens (see 3.2.5) which fits well with the observation that inflammation and…”