Complement Component Factor D/CFD/Adipsin
Complement Component Factor D/CFD, also known as adipsin, is a serine protease (SP) of about 24 kDa consisting of a single polypeptide of 228 amino acids. Unlike other SPs in the complement system, CFD circulates in the plasma as a mature but ‘resting-state’ form at a very low concentration and is synthesized mainly in adipocytes and macrophages. The human CFD shares 98%, 96%, 84%, and 66% amino acid sequence homology with the chimpanzee, rhesus monkey, porcine, and mouse protein, respectively.
The function of CFD is to cleave its sole substrate, factor B in Mg²⁺-dependent complex with C3(H2O) or C3b, to generate the alternative pathway C3 convertases C3(H2O)Bb and C3bBb. CFD is an important component of the complement alternative pathway and plays a vital role in the initiation and propagation of the alternative pathway of complement activation and in the amplification loop of C3 activation. CFD is expressed in a variety of tissues, including monocytes/macrophages, muscle, sciatic nerve, endometrium, kidney, intestine, and is particularly high in adipocytes. The expression level of CFD is reduced in various mouse models of obesity.
Fig.1 Activation of complement alternative pathway. (Shahini, 2017)
Preparation of CFD
CFD can be purified from human serum, but the procedures are cumbersome and the yield is low due to its low serum concentration. A simpler, higher yield method for obtaining relatively large amounts of CFD is to use urine from patients with Fanconi syndrome as a starting material. This method is suitable for purifying proteins from the peritoneal dialysate. At present, recombinant human CFD has been expressed from mammalian CHO and HEK293 cells in their secreted mature form and purified from the culture medium.
CFD Levels and Disease
The concentration of serum CFD is regulated by the catabolism in the kidney where CFD is filtered by the glomerulus and reabsorbed by the proximal tubule. In patients with renal failure, circulating levels of CFD are elevated. Similarly, in patients with Fanconi syndrome, a disorder in which the renal proximal tubule is impaired, the concentration of factor D in the urine is also highly elevated. Furthermore, CFD deficiency is related to the low activity of the alternative pathway and low capacity to opsonize bacteria. In patients with CFD gene mutation that causes complete CFD deficiency, recurrent bacterial infections are observed. In fact, people with CFD deficiency are rare and are phenotypically normal, but have an increased risk of infection, especially Neisseria meningitides.
CFD as A Therapeutic Target
CFD is an attractive therapeutic target because it is an alternative pathway-specific protease that circulates in the blood. CFD is mainly responsible for the conversion of the alternative pathway proconvertases C3bB to form the active C3 convertase C3bBb. In addition, it is the rate-limiting enzyme of the alternative pathway with the lowest plasma concentrations of all complement proteins. Therefore, targeting CFD with neutralizing anti-CFD antibodies is a promising therapeutic strategy to inhibit complement activation of the alternative pathway for the treatment of age-related macular degeneration. In addition to inhibiting alternative pathways, anti-CFD antibodies also indirectly block classical and mannose-bound lectin pathways, because the amplification of these pathways depends on the convertase activation of the alternative pathway.
Creative Biolabs offers high-quality complement component CFD related services and products, including:
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CFD Antibodies
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CFD Related Array Kits
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CFD Related Peptides
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CFD Related Lysates
If you would like more information, please feel free to contact us.
Reference
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Shahini, N.; et al. The alternative complement pathway is dysregulated in patients with chronic heart failure. Scientific reports. 2017, 7: 42532.
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