Allergic asthma is thought to be the result of an inappropriate specific immune response against common environmental antigens. However, studies of animal asthma models have also linked the innate immune system, in particular complement factors C3a and C5, to murine airway hyperresponsiveness. Because the possible role of these anaphylatoxins in patients with asthma is not understood, we tested the hypothesis that C3a and C5a will increase in the bronchoalveolar lavage (BAL) fluid of patients with asthma after segmental allergen provocation. In a group of 15 subjects with mild asthma we found a significant upregulation of C3a and C5a 24 h after allergen challenge compared with baseline values (p < 0.01). In a control group of healthy volunteers the concentrations remained basically unchanged. Furthermore, we found a strong correlation between both anaphylatoxins and the number of eosinophils (p < 0.01) and, to a lesser degree, with the number of neutrophils (p < 0.05) in BAL fluid. These data suggest a contribution of anaphylatoxins C3a and C5a to the pathogenesis in asthma. However, the pathogenic role of these substances in relation to asthma remains to be elucidated, for example, by using anaphylatoxin receptor blockers as a possible new therapeutic principle.
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http://dx.doi.org/10.1164/ajrccm.164.10.2010096 | 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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