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PMID: 1371955 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Structural properties of the glycoplasmanylinositol anchor phospholipid of the complement membrane attack complex inhibitor CD59.

Clinical and experimental immunology ·Vol. 87 ·No. 3 ·1992-03-00 ·Pages 415-21

Ratnoff WD, Knez JJ, Prince GM, Okada H, Lachmann PJ, Medof ME

Abstract

CD59, the membrane regulator of autologous C5b-9 channel formation, exhibits variable sensitivity to cleavage by phosphatidylinositol-specific phospholipase C (PI-PLC), an enzyme that releases glyco-inositolphospholipid (GPI)-anchored proteins from cell surfaces. To determine whether the GPI-anchor phospholipid of CD59 is similar to that of decay-accelerating factor (DAF) and whether variation in its structure underlies its variable enzyme susceptibility, the GPI anchors of the two proteins expressed on erythrocytes, polymorphonuclear and mononuclear leucocytes were compared in situ and after purification. Flow cytometric analyses of PI-PLC-treated cells showed parallel cell type specific release of both proteins as a function of enzyme concentration. Non-denaturing PAGE analyses of alkaline/hydroxylamine-treated proteins (affinity-purified from [125I]-surface-labelled cells) provided evidence for (i) comparable proportions of GPI-anchor acylation, and (ii) alkali-resistant rather than alkali-sensitive lipid substituents in erythrocytes. These findings argue that the differential C5b-9 sensitivity that distinguishes paroxysmal nocturnal haemoglobinuria II and III erythrocytes does not derive from expression of CD59 molecules with alternative GPI-anchor phospholipid structures.

MeSH Terms
Antigens, CD/chemistry Blood Proteins/chemistry CD55 Antigens CD59 Antigens Complement Inactivator Proteins/chemistry Complement Membrane Attack Complex/antagonists & inhibitors Electrophoresis, Polyacrylamide Gel Erythrocytes/drug effects Flow Cytometry Glycolipids/chemistry Glycosylphosphatidylinositols Humans Leukocytes, Mononuclear/drug effects Membrane Glycoproteins/chemistry Membrane Proteins/chemistry Neutrophils/drug effects Phosphatidylinositols/chemistry Structure-Activity Relationship Type C Phospholipases/pharmacology
Chemicals
Antigens, CD Blood Proteins CD55 Antigens CD59 Antigens Complement Inactivator Proteins Complement Membrane Attack Complex Glycolipids Glycosylphosphatidylinositols Membrane Glycoproteins Membrane Proteins Phosphatidylinositols Type C Phospholipases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Ratnoff W D
Institute of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106.
Knez J J
Prince G M
Okada H
Lachmann P J
Medof M E
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Article Info
Journal
Clinical and experimental immunology
Abbr.
Clin Exp Immunol
ISSN
0009-9104
Published
1992-03-00
Pages
415-21
Language
English
Region
England
NLM ID
0057202
PMCID
PMC1554345
Subset
IM
Grants
NIAID NIH HHS · AI23598 · United States
NIDDK NIH HHS · P01DK38181 · United States
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