Biomaterial Database

Amelioration of lytic abnormalities of paroxysmal nocturnal hemoglobinuria with decay-accelerating factor. 1985

M E Medof, and T Kinoshita, and R Silber, and V Nussenzweig

Purified decay-accelerating factor (DAF), from the stroma of normal human erythrocytes, was incorporated into the membranes of erythrocytes of patients with paroxysmal nocturnal hemoglobinuria (PNH), and its effect on the complement sensitivity of the cells was investigated. Reconstitution with exogenous DAF restored the ability of the affected PNH cells to resist assembly of the homologous C3 convertase, C4b2a, on their surfaces, and decreased the susceptibility of the cells to lysis in acidified serum. Conversely, treatment of normal erythrocytes with monoclonal or polyclonal anti-DAF antibodies abrogated the capacity of the normal cells to circumvent C4b2a assembly and rendered the cells sensitive to acid lysis. These findings show that the previously reported association of DAF deficiency with PNH is causally related to the lytic abnormalities of the cells and clarify the molecular basis for restriction of autologous convertase formation on normal human erythrocytes.

UI	MeSH Term	Description	Entries
D011951	Receptors, Complement	Molecules on the surface of some B-lymphocytes and macrophages, that recognize and combine with the C3b, C3d, C1q, and C4b components of complement.	Complement Receptors,Complement Receptor,Complement Receptor Type 1,Receptor, Complement
D001798	Blood Proteins	Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.	Blood Protein,Plasma Protein,Plasma Proteins,Serum Protein,Serum Proteins,Protein, Blood,Protein, Plasma,Protein, Serum,Proteins, Blood,Proteins, Plasma,Proteins, Serum
D003171	Complement Pathway, Classical	Complement activation initiated by the binding of COMPLEMENT C1 to ANTIGEN-ANTIBODY COMPLEXES at the COMPLEMENT C1Q subunit. This leads to the sequential activation of COMPLEMENT C1R and COMPLEMENT C1S subunits. Activated C1s cleaves COMPLEMENT C4 and COMPLEMENT C2 forming the membrane-bound classical C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.	Classical Complement Pathway,Classical Complement Activation Pathway,Complement Activation Pathway, Classical
D004912	Erythrocytes	Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.	Blood Cells, Red,Blood Corpuscles, Red,Red Blood Cells,Red Blood Corpuscles,Blood Cell, Red,Blood Corpuscle, Red,Erythrocyte,Red Blood Cell,Red Blood Corpuscle
D006457	Hemoglobinuria, Paroxysmal	A condition characterized by the recurrence of HEMOGLOBINURIA caused by intravascular HEMOLYSIS. In cases occurring upon cold exposure (paroxysmal cold hemoglobinuria), usually after infections, there is a circulating antibody which is also a cold hemolysin. In cases occurring during or after sleep (paroxysmal nocturnal hemoglobinuria), the clonal hematopoietic stem cells exhibit a global deficiency of cell membrane proteins.	Paroxysmal Cold Hemoglobinuria,Paroxysmal Nocturnal Hemoglobinuria,Marchiafava-Micheli Syndrome,Paroxysmal Hemoglobinuria,Paroxysmal Hemoglobinuria, Cold,Paroxysmal Hemoglobinuria, Nocturnal,Cold Paroxysmal Hemoglobinuria,Hemoglobinuria, Cold Paroxysmal,Hemoglobinuria, Nocturnal Paroxysmal,Hemoglobinuria, Paroxysmal Cold,Hemoglobinuria, Paroxysmal Nocturnal,Marchiafava Micheli Syndrome,Nocturnal Paroxysmal Hemoglobinuria,Syndrome, Marchiafava-Micheli
D006461	Hemolysis	The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity.	Haemolysis,Extravascular Hemolysis,Intravascular Hemolysis,Extravascular Hemolyses,Haemolyses,Hemolyses, Extravascular,Hemolyses, Intravascular,Hemolysis, Extravascular,Hemolysis, Intravascular,Intravascular Hemolyses
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000143	Acids	Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. (Grant & Hackh's Chemical Dictionary, 5th ed)	Acid
D050577	Complement C3-C5 Convertases	Serine proteases that cleave COMPLEMENT C3 into COMPLEMENT C3A and COMPLEMENT C3B, or cleave COMPLEMENT C5 into COMPLEMENT C5A and COMPLEMENT C5B. These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. Both cleavages take place at the C-terminal of an ARGININE residue.	C3 Convertase,C 3 Convertase,C3 Activator,C3-C5 Convertase,C5 Cleaving Enzyme,C5 Convertase,Complement 3 Convertase,Complement 5 Convertase,Complement C3 Convertases,Complement C5 Convertases,Activator, C3,C3 C5 Convertase,C3 Convertases, Complement,C3-C5 Convertases, Complement,C5 Convertases, Complement,Complement C3 C5 Convertases,Convertase, C 3,Convertase, C3,Convertase, C3-C5,Convertase, Complement 3,Convertases, Complement C3,Convertases, Complement C3-C5,Convertases, Complement C5
D018958	CD55 Antigens	GPI-linked membrane proteins broadly distributed among hematopoietic and non-hematopoietic cells. CD55 prevents the assembly of C3 CONVERTASE or accelerates the disassembly of preformed convertase, thus blocking the formation of the membrane attack complex.	Antigens, CD55,Decay-Accelerating Factor,CD55 Antigen,Complement Decay-Accelerating Factor,Complement Decay Accelerating Factor,Decay Accelerating Factor,Decay-Accelerating Factor, Complement