Neuromyelitis optica (NMO) is an autoimmune demyelinating disease of the central nervous system in which binding of anti-aquaporin-4 (AQP4) autoantibodies (NMO-IgG) to astrocytes causes complement-dependent cytotoxicity (CDC) and inflammation resulting in oligodendrocyte and neuronal injury. There is compelling evidence for a central role of complement in NMO pathogenesis. Here, we evaluated th...

C1 inhibitor is a heavily glycosylated plasma protein that regulates the activity of the first component of complement (Cl) by inactivation of the serine protease subcomponents, COr and Cls. C1 inhibitor cDNA clones have been isolated, and one of these (pClINH1, 950 base pairs) has been partially sequenced. Sequence analysis demonstrates that the C1 inhibitor is a member of the serpin "superfam...

Serum levels of the complement proteins C3, C4, C1 inhibitor (C1 INH), factor I (C3b inactivator) and factor H (BIH) and plasma levels of cleavage products of C3 (C3c) and factor B were measured in 26 patients with acute pancreatitis. Breakdown of C3 occurred in 19 patients, as shown by a reduction in C3 level and the presence of C3c. C4 levels, however, did not fall and factor B breakdown prod...

Hereditary angioedema (HAE) is known as a deficiency state of C1 inhibitor (C1 INH), an important protease inhibitor protein involved in the complement system. As with other components of the classical pathway of the complement system, a state of its deficiency often causes clinical immunoregulatory disorders. A 45-yr-old brother and a 63-yr-old sister with HAE both developed chronic renal fail...

angioedema secondary to c1 inhibitor deficiency has been rarely reported to be associated with systemic lupus erythematosus. a genetic defect of c1 inhibitor produces hereditary angioedema, which is usually presented with cutaneous painless edema, but edema of the genital area, gastrointestinal and laryngeal tracts have also been reported. in lupus patients, angioedema may be the result of an a...

Complement C1 is the defining component of the classical pathway. Within the C1qC1r2C1s2 complex, C1q functions as a molecular scaffold for C1r2C1s2 and C1q binding to its ligands activates these two serine proteases. The classic C1q ligands are antigen-bound antibodies and activated C1s cleaves C4 and C2 to initiate the complement cascade. Recent studies suggest broad C1 functions beyond the c...

Protease nexin I is a proteinase inhibitor that is secreted by human fibroblasts and forms stable complexes with certain serine proteinases; the complexes then bind to the fibroblasts and are rapidly internalized and degraded. In this report, we show that this inhibitor, which is present in very low concentrations in plasma, has functional and structural similarities to C1 inhibitor, an abundan...

C1 esterase inhibitor (C1-INH) can inhibit multiple pathways (complement, contact-kinin, coagulation, and fibrinolysis) that are all implicated in the pathophysiology of asthma. We explored the effect of human plasma-derived C1-INH on allergic lung inflammation in a house dust mite (HDM) induced asthma mouse model by daily administration of C1-INH (15 U) during the challenge phase. NaCl and HDM...

BACKGROUND Exposure of blood to artificial surfaces, as in cardiopulmonary bypass, induces an inflammatory response involving complement, leukocyte and platelet activation. To elucidate the specific role of complement in this process, studies were performed on blood circulated in polyvinyl chloride tubing in the absence and presence of complement inhibitors. Parallel experiments were performed ...

Several lines of experimental evidence have suggested that one or more peptides that can enhance vascular permeability may be released from the second component ofhuman complement, C2 (1-5) . This possibility is important to understanding the molecular mechanisms that lead to bouts of circumscribed edema to which persons with hereditary angioneurotic edema (HANE)' are susceptible. Persons with ...