Disease relevance of Complement Pathway, Classical

• Collectively, these results show that SK-MEL-170 human melanoma cells evade complement-mediated cytolysis despite sufficient activation of early components of the classical complement pathway by p65-mediated rapid degradation of surface-bound C3b, leading to a significant reduction in membrane attack complex formation [1].
• By using serum immunochemically depleted in the classical complement pathway component C4 and/or the alternative complement pathway component factor B, as well as other methods, it was shown that LCMV was inactivated via the classical complement pathway [2].
• Because EAC4bhu were lysed even by C2-deficient human serum, C3 convertase of the classical complement pathway would not be involved in the hemolysis of EAC4bhu [3].
• Paradoxically, genetic deficiencies of early components of the classical complement pathway (e.g., C1q, C4, and C2) are associated with an increased incidence of lupus in humans and lupus-like disease in murine knockout strains [4].
• In this paper we demonstrate the synthesis of the components of the classical complement pathway, namely C1q, C1r, C1s, C1-Inh, C2, C4, and C5, by human glioma cell lines (U118MG, T193, and T98G) [5].

Psychiatry related information on Complement Pathway, Classical

• Aspartate residue 7 in amyloid beta-protein is critical for classical complement pathway activation: implications for Alzheimer's disease pathogenesis [6].

High impact information on Complement Pathway, Classical

• C1-Inh, belonging to the superfamily of serine proteinase inhibitors (serpins), is a major inhibitor of the classical complement pathway, the contact activation system, and the intrinsic pathway of coagulation, respectively [7].
• Mannose-binding protein (MBP), C1q, the recognition component of the classical complement pathway, and pulmonary surfactant protein A (SP-A) are members of a family of molecules containing a collagen-like sequence contiguous with a noncollagen-like sequence, and usually having the properties of a lectin [8].
• C3 deposition on promastigotes activated through the classical complement pathway reaches a 50% maximum after similar50 s, and represents >85% of total C3 bound [9].
• The role of the classical complement pathway in humoral immune responses was investigated in gene-targeted C1q-deficient mice (C1qA-/-) [10].
• Using a functional assay that measures the surface deposition of C3 activated via the classical complement pathway, we show that Crry/p65-expressing cells have a markedly decreased amount of C3 deposited on them as compared with control cells expressing the antisense construct or cells expressing MCR1 or MCR2 [11].

Chemical compound and disease context of Complement Pathway, Classical

• We found that activation of the classical complement pathway up to C5 was sufficient to neutralize HSV-2 gC-null virus by HSV antibody-negative human serum [12].
• Legionella pneumophila lipopolysaccharide activates the classical complement pathway [13].
• A purified preparation of Epstein-Barr virus (EBV) has been shown to activate the classical complement pathway by direct interaction with the first component of complement, C1, without the intervention of antibody [14].
• When lizard serum was chelated with 10 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid plus 4 mM MgCl2 to block only classical complement pathway activation, >85% of spirochetes were immobilized within 1 hr [15].

Biological context of Complement Pathway, Classical

• Presumably, the latter molecules are unable to interact in their native state with C1 in the manner required for initiation of the classical complement pathway, possibly due to the configurational inaccessibility of the entire C1 binding site [16].
• In the stable transfected cell lines, C4A and C4B are synthesized, undergo a complex series of post-translational modifications, and each functions appropriately in activation of the classical complement pathway [17].
• C1q-deficient mice and factor B- and C2-deficient mice, deficient in the classical complement pathway and in both the alternative and classical complement activation pathways, respectively, exhibited only a slight delay in the resolution of the acute phase of parasitemia [18].
• Mouse complement-dependent opsonization of sensitized erythrocytes, as judged by macrophage complement receptor-mediated attachment and phagocytosis of the erythrocytes, was comparably inhibited by sodium azide, suggesting that azide acted within the sequence of the first four components of the classical complement pathway [19].
• These data suggest that the hydrolysis of PGA to glycolide activates the classical complement pathway [20].

Anatomical context of Complement Pathway, Classical

• We have previously provided evidence that suggests that exposure of cryostat skin sections to normal human serum (NHS) results in the antibody-independent Clq binding to cytoplasmic structures of various cell types, leading to classical complement pathway activation as evidenced by cytoplasmic C3 deposition [21].
• In the present study, we show that the defensin human neutrophil peptide-1 (HNP-1) is able to inhibit activation of the classical complement pathway by inhibition of C1q hemolytic activity [22].
• C1q, a plasma glycoprotein and the recognition component of the classical complement pathway, interacts with specific cells of the immune system resulting in the enhancement of cell function [23].
• FJ-h Ags purified from K562 and U937 cells displayed inhibitory activity in the functional EAC14 assay for the classical complement pathway, as did urine FJ, and they were recognized immunochemically by five different (one polyclonal and four monoclonal) anti-FJ Abs [24].
• Although antibodies specific for three cell wall epitopes were capable of inducing complement-cell wall complex formation by the classical complement pathway, only anti-A polysaccharide antibody (N-acetyl-D-glucosamine epitope) was effective by the alternative complement pathway [25].

Associations of Complement Pathway, Classical with chemical compounds

• Activation of the classical complement pathway on the membrane of autologous cells results in the deposition of C4b on their surface and in the assembly of the C3 convertase C4b2a, one of the amplifying enzymes of the cascade [26].
• Studies using genetically C2-deficient serum and purified C2 indicate that the classical complement pathway is primarily involved in the solubilization, however, there may be minor involvement by the alternative pathway [27].
• C1 fixation and classical complement pathway activation by a fragment of the Cmu4 domain of IgM [28].
• Covalent association of C3b with C4b within C5 convertase of the classical complement pathway [29].
• Activation of the classical complement pathway by mannose-binding protein in association with a novel C1s-like serine protease [30].

Gene context of Complement Pathway, Classical

• Complement C4 is a highly polymorphic protein essential for the activation of the classical complement pathway [31].
• Binding of C1q to immobilized PTX3 induced activation of the classical complement pathway as assessed by C4 deposition [32].
• Mannose-binding lectin (MBL) is a serum protein that has been demonstrated to activate the classical complement pathway and to function directly as an opsonin [33].
• The C1q-deficient mice lack the classical complement activation pathway [34].
• C4b-binding protein (C4BP) is a regulator of the classical complement pathway, acting as a cofactor to factor I in the degradation of C4b [35].

Analytical, diagnostic and therapeutic context of Complement Pathway, Classical

• By Western blotting, we showed that the protein levels of CRP and complement proteins were also up-regulated in plaque tissue and that there was full activation of the classical complement pathway [36].
• In this study, we demonstrate that mice lacking MBL, and hence are devoid of MBL-dependent lectin pathway activation but have fully active alternative and classical complement pathways, are protected from cardiac reperfusion injury with resultant preservation of cardiac function [37].
• The administration of protamine to patients undergoing cardiopulmonary bypass (CPB) to neutralize heparin and to reduce the risk of bleeding, induces activation of the classical complement pathway mainly by heparin-protamine complexes [38].
• Complement component C3b, immobilized as a result of classical complement pathway activation in the presence of TPO/TPO-ab complexes in vitro, was measured by ELISA [39].
• In this study, six of the nine toothpastes tested activated the classical complement pathway, leading to C3 cleavage, as determined by crossed immunoelectrophoresis [40].

References