Decay-Accelerating Factor and Membrane Cofactor Protein

  • D. M. Lublin
  • J. P. Atkinson
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 153)


Cells exposed to plasma proteins are frequently under attack from the complement system. This can arise either as a bystander process to the classical or alternative pathways of activation initiated during the immune response to foreign particles and organisms or from the constant tick-over of the alternative pathway. Thus, it is critical for the cell to regulate the complement pathway on its own surface. The plasma proteins, H and C4 binding protein (C4bp), in conjugation with the serine protease I, function to this end. Additionally, cells possess a number of membrane proteins to regulate complement deposited on their surfaces; the largest group, focused on C3 and the C3 convertases, consists of the C3b/C4b receptor (CR1), decay-accelerating factor (DAF), and membrane cofactor protein (MCP). CR1, although it has both decay-accelerating activity and serves as a cofactor for the I-mediated cleavage of C3b and C4b, acts mainly extrinsically as a receptor for C3b-bearing immune complexes. DAF exerts its decay-accelerating activity intrinsically on the cell itself (see below). Indeed, the lack of DAF in the membrane of blood cells in the disease paroxysmal nocturnal hemoglobinuria (PNH) leads to an increased complement sensitivity of these cells. Purified MCP can also regulate C3 and the C3 convertases through cofactor I activity. MCP has the same approximate size and overall structure as DAF, and hence it might also function intrinsically to control C3 convertases formed on the same cell. This chapter reviews in detail the structure, both at the protein and DNA levels, of these two complement regulatory membrane glycoproteins, DAF and MCP, and discusses their physiological roles in protecting cells from damage by autologous complement.


Paroxysmal Nocturnal Hemoglobinuria Membrane Cofactor Protein Cofactor Activity Complement Regulatory Protein Paroxysmal Nocturnal Hemoglobinuria Patient 
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Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • D. M. Lublin
    • 1
  • J. P. Atkinson
    • 2
  1. 1.Division of Laboratory Medicine, Departments of Pathology and MedicineWashington University School of MedicineSt. LouisUSA
  2. 2.Division of Rheumatology, Department of Medicine, and Howard Hughes Medical Institute LaboratoriesWashington University School of MedicineSt. LouisUSA

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