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Intravascular haemolysis is a physiological phenomenon as well as a severe pathological complication when accelerated in various autoimmune, infectious (such as malaria) and inherited (such as sickle cell disease) disorders. Haemoglobin released into plasma is captured by the acute phase protein haptoglobin, which is depleted from plasma during elevated(More)
The covalent binding of complement components C3 and C4 is critical for their activities. This reaction is made possible by the presence of an internal thioester in the native protein. Upon activation, which involves a conformational change initiated by the cleavage of a single peptide bond, the thioester becomes available to react with molecules with(More)
The activated form of the third complement protein, C3b, forms a stable complex with components of plasma membranes and particulate entities such as zymosan. The complex resists the action of detergents and protein denaturants as well as extremes of temperature, salt concentration, and pH. It can, however, be broken by exposure to hydroxylamine or by(More)
LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) are members of the beta2 integrins involved in leukocyte function during immune and inflammatory responses. We aimed to determine a minimized beta2 subunit that forms functional LFA-1 and Mac-1. Using a series of truncated beta2 variants, we showed that the subregion Q23-D300 of the beta2 subunit is sufficient to(More)
Leucocyte adhesion deficiency (LAD) is a hereditary disorder caused by mutations in the CD18 (beta2 integrin) gene. Four missense mutations have been identified in three patients. CD18(A270V) supports, at a diminished level, CD11b/CD18 (Mac-1, alphaMbeta2 integrin) and CD11c/CD18 (p150,95, alphaXbeta2 integrin) expression and function but not CD11a/CD18(More)
The antibodies Ki-M8, Ber-Mac3, GHI/61 and SM4 define a human macrophage-associated antigen with a relative molecular mass of 130,000 which we designate M130. The protein was purified by immunoaffinity chromatography and an N-terminal and three internal amino acid sequences were obtained. A cDNA fragment was initially obtained by polymerase chain reaction(More)
The covalent binding of C3 to target molecules on the surfaces of pathogens is crucial in most complement-mediated activities. When C3 is activated, the acyl group is transferred from the sulfhydryl of the internal thioester to the hydroxyl group of the acceptor molecule; consequently, C3 is bound to the acceptor surface by an ester bond. It has been(More)
In the leukocyte adhesion deficiency (LAD)-1 syndrome, there is diminished expression of beta2(CD18) integrins. This is caused by lesions in the beta2-subunit gene and gives rise to recurrent bacterial infections, impaired pus formation, and poor wound healing. We describe a patient with clinical features compatible with a moderately severe phenotype of(More)
A remarkable difference has been observed between the reactivity of the two forms of human complement component C4. C4B binds twice as effectively as C4A to antibody-coated red cells, but the reverse occurs with protein-antigen complexes. C4B reacts much more effectively with hydroxyl groups than C4A and this is reversed for reaction with amino groups in(More)
A key step in the elimination of pathogens from the body is the covalent binding of complement proteins C3 and C4 to their surfaces. Proteolytic activation of these proteins results in a conformational change, and an internal thioester is exposed which reacts with amino or hydroxyl groups on the target surface to form amide or ester bonds, or is hydrolysed.(More)