Complement system activation was investigated in two girls with familial homozygous hypercholesterolemia undergoing two monthly sessions on LA15 or LA40 (Kaneka liposorber). We determined blood levels of C3c and C3a, leukocyte counts, and plasma levels of C3c and C3a in the extracorporeal circulation device at the start of the sessions and 15 and either 60 or 120 min into them. Sequential eluates were collected from LA40 at the end of the sessions (0.5M NaCl, 1M hydroxylamine). Anaphylatoxin C3a increased throughout, especially with LA40. As previously reported, C3a was trapped in the dextran column but was noticeably present in efferent plasma. Besides many proteins, nonnative complement fragments bearing C3a and C3d antigens were detected in almost all the eluates, suggesting possible in situ complement activation. Practically, complement activation induced by the first filter is a risk; long-term side effects may arise from this extracorporeal circulation device.
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Arch Dermatol Res
January 2025
Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, 9 Dongdan 3rd Alley, Beijing, 100730, China.
Bullous pemphigoid (BP) is a debilitating autoimmune skin blistering disease, characterized by the deposition of specific autoantibodies at the dermal-epidermal junction. This leads to an inflammatory cascade involving the activation of complement proteins, mast cell degranulation, immune cell recruitment, and the release of proteases by granulocytes. While several cytokines and signaling pathways have been implicated in the pathogenesis of BP, the precise mechanism behind autoantibody production remains unclear.
View Article and Find Full Text PDFVaccines (Basel)
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Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon 24341, Republic of Korea.
Messenger RNA (mRNA)-based therapeutics have shown remarkable progress in the treatment and prevention of diseases. Lipid nanoparticles (LNPs) have shown great successes in delivering mRNAs. After an mRNA-LNP vaccine enters a cell via an endosome, mRNA is translated into an antigen, which can activate adaptive immunity.
View Article and Find Full Text PDFCurr Issues Mol Biol
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Children & Adolescent Hematology-Oncology Unit, Second Department of Pediatrics, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Immune thrombocytopenia (ITP) in pediatric patients is a common cause of isolated thrombocytopenia. Various pathophysiological mechanisms are implicated in ITP pathogenesis, including the production of autoantibodies against components of platelets (PLTs) by B-cells, the activation of the complement system, phagocytosis by macrophages mediated by Fcγ receptors, the dysregulation of T cells, and reduced bone marrow megakaryopoiesis. ITP is commonly manifested with skin and mucosal bleeding, and it is a diagnosis of exclusion.
View Article and Find Full Text PDFFront Immunol
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The First Affiliated Hospital of Army Military Medical University, Department of General Surgery, Chongqing, China.
Gastric cancer continues to be a leading global health concern, with current therapeutic approaches requiring significant improvement. While the disruption of iron metabolism in the advancement of gastric cancer has been well-documented, the underlying regulatory mechanisms remain largely unexplored. Additionally, the complement C5a-C5aR pathway has been identified as a crucial factor in gastric cancer development.
View Article and Find Full Text PDFNat Struct Mol Biol
January 2025
Department of Molecular Biology and Genetics, Aarhus, Denmark.
The C3 protein is the central molecule within the complement system and undergoes proteolytic activation to C3b in the presence of pathogens. Pattern-independent activation of C3 also occurs via hydrolysis, resulting in C3(HO), but the structural details of C3 hydrolysis remain elusive. Here we show that the conformation of the C3(HO) analog, C3MA, is indistinguishable from C3b.
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