In recent years a plethora of data has accumulated directing toward an important role of polypeptides C3a and C5a and its degradation product C5adesArg, summarized as anaphylatoxins (ATs), in microbial host defense and immune regulation. The ATs exert their various biologic functions by interacting with specific C3a- and C5a-receptors present on cells of myeloid origin, epithelial cells, smooth muscle cells as well as on activated B- and T-cells. Activation of AT receptors mediates signal transduction pathways triggering a variety of proinflammatory events. However, by interacting with the cytokine- and chemokine network C3a and C5a exhibit also anti-inflammatory properties. In this review the focus is on the pathogenetic role of the ATs in sepsis, immune complex disease, delayed type hypersensitivity and asthma. Discussed are data from animal models in which the ATs are blocked by specific C3a or C5a inhibitors or from mice with genetic deletions of the specific receptors of either C3a or C5a/C5adesArg.
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http://dx.doi.org/10.1016/s0161-5890(01)00041-4 | DOI Listing |
Int Immunopharmacol
January 2025
Immunochemistry Laboratory, Butantan Institute, São Paulo, SP, Brazil; Center of Toxins, Cell Signaling and Immune Response (CeTICS), CEPID, FAPESP, Brazil. Electronic address:
The complement system plays a crucial role in various pathophysiological conditions, including snake envenomation. In this study, we investigated the effects of Bitis arietans venom on the complement system using an ex vivo human whole blood model. Our findings demonstrate that B.
View Article and Find Full Text PDFPediatr Nephrol
January 2025
Consejo Nacional de Investigaciones Científicas y Técnicas, CONICET, Buenos Aires, Argentina.
Background: This research explores complement activation products involvement and risk and protective polymorphisms in the complement alternative pathway genes in Shiga toxin-associated hemolytic uremic syndrome (STEC-HUS) pathogenesis.
Methods: We analyzed the levels of complement activation products, C3a, C5a and soluble C5b-9 (sC5b-9) and plasma concentrations of Factor H (FH) and FH-related protein 1 (FHR-1) in 44 patients with STEC-HUS, 12 children with STEC-positive diarrhea (STEC-D), and 72 healthy controls (HC). STEC-HUS cases were classified as "severe" or "non-severe".
J Virol
January 2025
University of Central Florida, College of Medicine, Orlando, Florida, USA.
Unlabelled: Persistent viral infections can be an important medical problem, with persistently infected (PI) cells extending viral shedding, maintaining inflammation, and providing potential sources for new viral variants. Given that PI cells can acquire resistance to some innate immune pathways, we tested the hypothesis that complement (C')-mediated lysis of parainfluenza virus 5 (PIV5)-infected cells would differ between acute-infected and PI cells. Biochemical and real-time cell viability assays showed effective C'-mediated lysis of A549 lung cells acutely infected with PIV5, through pathways that depended on C3 and C5, but largely independent of C6.
View Article and Find Full Text PDFInvest Ophthalmol Vis Sci
January 2025
Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Purpose: In the aging retina, persistent activation of microglia is known to play a key role in retinal degenerative diseases like age-related macular degeneration (AMD). Furthermore, dysregulation of the alternative complement pathway is generally accepted as the main driver for AMD disease progression and microglia are important producers of local complement and are equipped with complement receptors themselves. Here, we investigate the involvement of anaphylatoxin signaling, predominantly on Iba1+ cell activity, in light-induced retinal degeneration as a model for dry AMD, using anaphylatoxin receptor knockout (KO) mice.
View Article and Find Full Text PDFNeurol Neuroimmunol Neuroinflamm
March 2025
Department of Neurology with Institute of Translational Neurology, University Hospital 4 Münster, Germany.
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