Complement regulatory proteins

ApoJ is another protein component of HDL which is highly expressed by the RPE and neural retina, especially under oxidative stress conditions (Wong et al., 2000, 2001). It can act as a complement regulatory protein, which by binding to and inactivating the membrane-attack complex can prevent cytolysis (Bartl et al., 2001). ApoJ accumulation was identified in drusen in AMD patients (Sakaguchi et al., 2002 Wong et al., 2000). 

CD59 Cluster of differentiation 59, a complement regulatory protein... 

The selectins are a family of vascular cell surface receptors that are characterized by lectin-like domains at their amino termini, an adjacent epidermal growth factorlike domain, followed by multiple, short consensus repeat units homologous to those of the complement regulatory proteins. Platelet express P-selectin (CD62 ... 

Bora NS, Gobleman CL, Atkinson IP, Pepose IS, Kaplan HI (1993) Differential expression of the complement regulatory proteins in the human eye. Invest Ophthalmol Vis Sci 34 3579—3584. 

Complement regulatory protein CD55 Bilateral renal pedicle clamping No. Worse AKI [179]... 

B. (1989). Endothelial leukocyte adhesion molecule 1 an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science 243, 1160-1165. 

Fig. 6.12 Peptide domains and attached glycosaminoglycans in aggrecan and versican. HABR Hyaluronic Acid-Binding Region GAG Glycosaminoglycan-Attachment domain EGF Epidermal Growth Factor-like repeat LEC C-type Lectin-like module C (yellow) Complement regulatory protein-like module (see text) (From GlycoWord website http //www.glycoforum. gr.jp/science/word/proteoglycan/PGA03E.html (contributed by Toshikazu Yada))...

GPI-deficient mammalian cells are viable in tissue culture and many GPI-deficient mutant cell lines have been established. However, GPI deficiency has major consequences at the level of tissues and the whole body. This was revealed in transgenic mouse models in which the PIG-A gene (required for the first step of GPI biosynthesis) was knocked out in specific tissues or in the whole animal. For example, keratinocyte-specific disruption of PIG-A caused abnormal development of skin leading to death of the mutant mice a few days after birth (M. Tarutani, 1997), and disruption of PIG-A in the whole animal resulted in embryos that did not develop beyond day 9 of gestation (M. Nozaki, 1999). A somatic mutation of PIG-A in multipotent hematopoietic human stem cells causes paroxysmal nocturnal hemoglobinuria, an acquired hemolytic disease in humans characterized by abnormal activation of complement on erythrocytes due to a deficiency of GPI-anchored complement regulatory proteins such as decay accelerating factor (N. Inoue, 2003). This disease is characterized by intravascular hemolysis and anemia. 

Deppenmeier, S. et al.. Health status of transgenic pigs expressing the human complement regulatory protein CD59, Xenotransplantation, 13, 345, 2006. 

Caswell CC, Han R, Hovis KM et al. The Sell protein of M6-type group A Streptococcus binds the human complement regulatory protein, factor H and inhibits the alternative pathway of complement. Mol Microbiol 2008 67(3) 584-596. 

Madico G, Welsch JA, Lewis LA et al. The meningococcal vaccine candidate GNA1870 binds the complement regulatory protein factor H and enhances serum resistance. J Immunol 2006 177 501-510. 

Macromolecules that are GPI anchored rely on the anchor for cell surface expression. Thus, defects in GPI anchoring can have severe consequences if they cause non-expression of functionally critical macromolecules. A well documented example is paroxysmal nocturnal hemoglobinuria (PNH), a human disease caused by a GPI biosynthesis defect in affected blood cells leading to the non-expression of complement regulatory proteins [4]. 

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