Complement factors

Cl-Inh belongs to a superfamily of serine protease inhibitors (serpins) and is a major inhibitor of F-XIIa and kallikrein. It is also an inhibitor of activated complement factors C1 q, C1 r, and C1 s. C1 -Inh thus regulates the activation of two important plasma cascade systems. Proteases induce a conformational change in the plasma protein a2-M, which results in entrapment of the protease into the a2-M cage (B4). In vivo, a2-M acts as a second inhibitor of kallikrein. 

The classical pathway can become activated by immune complexes, bacteria, viruses, and F-XIIa. Binding occurs to the complement C1 q, a part of complement factor 1 (Cl). This initiates a cascade of activations, first of Clr, Cls, then of C4. This C4 activates C2, after which C3 becomes activated. Activated C3 initiates a cascade of activations, which are in common with the alternative pathway and which end up in activated C5-9, a membrane attack complex that lyses the target. 

Bladder tumor-associated antigen (BTA), a human complement factor H, is produced by bladder cancer cells (men two to three times as often as women). Cancer cells are sometimes seen in urine samples by microscope cytoscopy (examination of the bladder with an instrument inserted into the urethra), which can reveal abnormal areas. Biopsy is needed to confirm the diagnosis. Early stage cancer confined to the bladder wall can often be removed with a cytoscope. If several tumors are present, they are removed by infusing the bladder with a solution containing bacteria able to stimulate the immune system. 

RPE cells can express a number of anti-inflammatory and pro-inflammatory cytokines, and complement factors constitutively and/or upon stimulation (Chen et al., 2007 Crane et al., 2000a Ebihara et al., 2007 Holtkamp et al., 2001 Joffre et al., 2007). Therefore the effects of carotenoids on inflammatory responses are of great relevance to the retina. 

Chen, M, Forrester, JV, and Xu, H, 2007. Synthesis of complement factor H by retinal pigment epithelial cells is down-regulated by oxidized photoreceptor outer segments. Exp Eye Res 84, 635-645. 

Wiggs, JL, 2006. Complement factor H and macular degeneration—The genome yields an important clue. Arch Ophthalmol 124, 577-578. 

Complement factor H and platelet-activating factor acetylhydrolase polymorphisms and hemolytic uremic syndrome due to E. coli 0157... 

Ying L, Katz Y, Schlesinger M et al. Complement factor H gene mutation associated with autosomal recessive-atypical hemolytic uremic syndrome. Am J Hum Genet 1999 65[6] 1538—1546. 

Unlu M et al. Detection of complement factor B in the cerebrospinal fluid of patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy disease using two-dimensional gel electrophoresis and mass spectrometry. Neurosci Lett 2000 282 149-152. 

Walters, D.M., et al., Complement factor 3 mediates particulate matter-induced airway hyperresponsiveness, Am. J. Respir. Cell. Mol. Biol. 27,4, 413, 2002. 

The effects of Lp(a) on the fibrinolytic system are based on the homology between plasminogen and Lp(a) (E3, E5, K4). Inactive Glu-plasminogen is converted to inactive glutamine-plasmin or inactive lysine-plasmin. Both can be converted to active lysine-plasmin, the activity of which is based on the serine protease part that splits fibrin and fibrinogen, but also factors V and Villa. In addition, Lp(a) is able to activate factor XII, factor VII, and the complement factors Cl and C3. 

Technically, in vitro transcription is achieved from standard expression plasmids typically carrying SP6 or T7 promoters using marketed kits. Translation into the polypeptide may be either coupled directly to the transcription (in vitro TnT) or require isolation of the RNA. Again, a large number of suitable prokaryotic and eukaryotic cell extracts as well as complementation factors are freely available. 

In healthy individuals, the concentration of plasma proteins is constant. Diseases in organs that are involved in protein synthesis and breakdown can shift the protein pattern. For example, via cytokines (see p. 392), severe injuries trigger increased synthesis of acute-phase proteins, which include C-reac-tive protein, haptoglobin, fibrinogen, complement factor C-3, and others. The concentrations of individual proteins are altered in some diseases (known as dysproteinemias). 

The complement system is part of the innate immune system (see p. 294). It supports nonspecific defense against microorganisms. The system consists of some 30 different proteins, the "complement factors," which are found in the blood and represent about 4% of all plasma proteins there. When inflammatory reactions occur, the complement factors enter the infected tissue and take effect there. 

Chemotaxis. Various complement factors attract immune cells that can attack and phagocytose pathogens. 

Opsonization. Certain complement factors ( opsonins ) bind to the pathogens and thereby mark them as targets for phagocytos-ing cells (e.g., macrophages). 

Membrane attack. Other complement factors are deposited in the bacterial membrane, where they create pores that lyse the pathogen (see below). 

Complement components—Clr, Cl and C2 Complement factors—B, D and I Cytotoxic cell proteases—granzymes A to H Mast cell proteases—... 

Klein RJ, Zeiss C, Chew EY et al. Complement factor H polymorphism in age-related macular degeneration. Science 2005 308 385-389. 

Ellipsometry can follow the interactions between two types of biological macromolecules, the first of those two bound physically to the surface, the other acting from the solution. The binding of conconavalin A to adsorbed mannan 180) and of cholera toxin to adsorbed ganglioside t83) are examples. The adsorption of complement factors to an antibody-coated surface was monitored by ellipsometry and a modification of the same method was used for quantification of migration inhibition of human polymorphonuclear leucocytes 182). Interaction of proteins and cells with affinity ligands covalently coupled to silicon surfaces has been also studied 183). 

Mandecki, W., Powell, B.S., Mollison, K.W., Carter, G.W. Fox, J.L. (1986). High-level expression of a gene encoding the human complement factor C5a in Escherichia coli. Gene 43, 131-8. 

W7. Wilson, C., C-reactive protein, antiproteases and complement factors as objective markers of severity in acute pancreatitis. Br. J. Surg. 76, 177 (1989). 

Korhonen, H., Marnila, P., and Gill, H.S. 2000a. Milk immunoglobulins and complement factors. Br. J. Nutr 84, S75-S80. 

Complement-mediated binding may occasionally be a cause of background in frozen tissue when whole antisera are used. However by the time large pools of antisera have been prepared for use, several of the complement factors are usually inactivated. 

Soluble Serum, interstitial fluid, urine, CSF, other body fluids Cytokines, chemokines, complement factors, shed tumor antigens Little to unknown... 

Light-dependent inactivation of EGF-R of complement factor 5a binding antitumour, immunosuppressive]... 

Before the characterization of chemokines the largest protein chemoattractant known was complement factor 5a. Complement protein 5 is proteolytically processed by the complement system during inflammation. 

Whistler, J. L., Gerber, B. O., Meng, E. C., Baranski, T.J., von Zastrow, M., and Bourne, H. R. (2002). Gonstitutive activation and endocytosis of the complement factor 5a receptor Evidence for multiple activated conformations of a G protein-coupled receptor. Traffic 3, 866-877. 

---