Factor D

Abstract

The complement system, which plays a major role in innate immune system, acts rapidly on the recognition and elimination of foreign bodies such as bacteria and viruses. The main roles of the complement system in innate immunity are foreign body labeling (opsonization), induction of leukocyte recruitment, through anaphylatoxin release, to the site of infection and inflammation, and destruction of foreign bodies by the formation of the membrane attack complex (MAC). 1 In recent years, it has been clarified that the complement system also plays a bridging role in exerting the effector functions of B cells and T cells that support acquired immunity. 2The complement system can be activated via three distinct pathways: the classical pathway (CP), the lectin pathway (LP), and the alternative pathway (AP). 3 The CP is initiated on antigenantibody complexes by the binding of C1q to Fc portion of IgM or IgG, followed by activation of the serine proteases C1r and C1s in a complex with C1q. 4 Since the CP is initiated by recognizing antigen-antibody complexes that are a hallmark of the adaptive immune response, it is considered that it emerged as a result of co-evolution of innate and acquired immunity. On the contrary, the LP is initiated on the surface of microorganisms or other targets by the binding of LP-pattern recognition molecules (LP-PRMs; mannose-binding lectin (MBL), collectin-10 (CL-10 or collectin liver

Transcriptome Analysis of Compensatory Growth and Meat Quality Alteration after Varied Restricted Feeding Conditions in Beef Cattle

“…In turn, complement components, through binding with C3a and C5a to their receptors C3aR and C5aR, respectively, promote triglyceride (TG) formation by inhibiting fat breakdown, enhancing Glc and FFA absorption, and indirectly reducing FFA release [ 39 , 40 , 41 ]. Adipose tissue cells also produce various complement factors, such as factor D (adipsin, CFD ), factor B ( CFB ), factor H ( CFH ), and C3 [ 38 , 42 , 43 ]. Additionally, the complement system can influence food intake and energy expenditure by acting on the central nervous system [ 44 ].…”

Quantification of the zymogenicity and the substrate-induced activity enhancement of complement factor D

“…When inhibiting FD, though, one must consider the high turnover rate of this small protein ( 46 ) and the observation that a relatively low amount of FD was enough to maintain AP activity ( 47 ). Another approach is to target MASP-3, which is present mostly as an active enzyme in the blood ( 48 ) and serves as the physiological FD maturase enzyme ( 21 , 22 , 49 ). Using a recombinant monoclonal antibody that binds to and inhibits MASP-3, AP inhibition could be attained in mice and cynomolgus monkeys in a few days after dosing due to pro-FD accumulation in the blood ( 50 , 51 ).…”

The complement alternative pathway in health and disease—activation or amplification?

“…In their review of FD, Sekine et al 8 address a fundamental challenge that has recently given rise to some controversy, the nature of circulating FD. For the AP/AL to function as an “oven‐ready” surveillance mechanism as envisaged in the tickover hypothesis, sufficient FD must circulate in the active form for its activity not to be rate limiting.…”