background: inappropriate activation or blockage of the inhibition of complement system could cause tissue damages in autoimmune diseases particularly rheumatoid arthritis (ra). defect in complement component regulation may cause damages to tissues, on the other hand, or the damaged tissue might affect the unnecessary activation of complement components.   objective: to investigate the expressi...

Background: Inappropriate activation or blockage of the inhibition of complement system could cause tissue damages in autoimmune diseases particularly rheumatoid arthritis (RA). Defect in complement component regulation may cause damages to tissues, on the other hand, or the damaged tissue might affect the unnecessary activation of complement components.   Objective: To investigate the expressi...

CD59, an 18-20-kD complement inhibitor anchored to the membrane via glycosyl phosphatidylinositol (GPI), can induce activation of T cells and neutrophils upon cross-linking with antibody. GPI-anchored molecules cocluster in high mol wt detergent-resistant complexes containing tyrosine kinases that are implicated in the signaling pathway. Exogenous, incorporated GPI-anchored molecules are initia...

Cholesterol-dependent cytolysins (CDCs) are a family of pore-forming toxins that punch holes in the outer membrane of eukaryotic cells. Cholesterol serves as the receptor, but a subclass of CDCs first binds to human CD59. Here we describe the crystal structures of vaginolysin and intermedilysin complexed to CD59. These studies, together with small-angle X-ray scattering, reveal that CD59 binds ...

Several groups have recently described the isolation of a 20 kDa membrane-attack-complex (MAC)-inhibiting protein, termed 'CD59 antigen', from human erythrocyte membranes. Antibodies raised against erythrocyte CD59 antigen detect antigen on the surface of many other cell types, and in some of these cells the antigen has been shown to have a molecular mass similar to that of the erythrocyte prot...

Obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH) during transient cessation of breathing, triples the risk for cardiovascular diseases. We used a phage display peptide library as an unbiased approach to investigate whether IH, which is specific to OSA, activates endothelial cells (ECs) in a distinctive manner. The target of a differentially bound peptide on ECs collecte...

Naegleria fowleri, the causative agent of primary amebic meningoencephalitis, is resistant to complement lysis. The presence of a complement regulatory protein on the surface of N. fowleri was investigated. Southern blot and Northern blot analyses demonstrated hybridization of a radiolabeled cDNA probe for CD59 to genomic DNA and RNA, respectively, from pathogenic N. fowleri. An 18-kDa immunore...

We demonstrate here that CD59, an inhibitor of the membrane attack complex (MAC) of the complement system, is present in cell-free seminal plasma (SP) at a concentration of at least 20 micrograms/ml. Analyses by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blotting, and Edman degradation indicated that this protein, SP CD59, was similar, if not identical, to CD59 isolated ...

The genetic defect underlying paroxysmal nocturnal hemoglobinuria (PNH) has been shown to reside in PIGA, a gene that encodes an element required for the first step in glycophosphatidylinositol anchor assembly. Why PIGA-mutated cells are able to expand in PNH marrow, however, is as yet unclear. To address this question, we compared the growth of affected CD59(-)CD34(+) and unaffected CD59(+)CD3...

Viruses of different families encode for regulators of the complement system (RCAs) or acquire such RCAs from the host to get protection against complement-mediated lysis (CML). As hepatitis C virus (HCV) shares no genetic similarity to any known RCA and is detectable at high titers in sera of infected individuals, we investigated whether HCV has adapted host-derived RCAs to resist CML. Here we...