ABSTRACT
144Complement, an integral part of the innate immune system, is a complex cascade of interacting proteins, some of which are soluble serum proteins, whereas others are membrane-anchored receptor proteins (Fearon, 1997, 1998; Hoffmann et al., 1999; Mayilyan et al., 2008). Complement can be activated by a variety of complex molecules, such as antigen–antibody complexes, aggregated antibody, endotoxin (lipopolysaccharide), complex sugars, and nucleic acids. The activation of complement can occur through one or more of three activation pathways, the classical pathway (CP), alternative pathway (AP), and lectin pathway (LP), and leads to an inflammatory response in the host. Activation involves enzymatic cleavage of several complement proteins with the generation of bioactive peptides that initiate a variety of immune reactions, including opsonization of targets and enhancement of phagocytosis, removal of antigen–antibody complexes, lysis of target cells, and stimulation of antibody production by B lymphocytes. The last is the mechanism by which complement is the bridge between the innate and adaptive immune system. The activation of complement is regulated and limited by a complex system of control proteins. Many complement components and their regulators are structurally and functionally similar and have arisen by gene duplication and in many instances contain structural domains/motifs that are also found in noncomplement proteins. A complement system and/or one or more complement components were described for vertebrate and invertebrate species across the phylogenetic spectrum. A lytic complement system composed of functionally distinct components and with activation properties of the mammalian CP was first demonstrated in serum of the nurse shark, Ginglymostoma cirratum (Jensen et al., 1981). Later, functional studies showed the involvement of complement-derived peptides in opsonization, chemotaxis, and anaphylaxis. Over the last decade, several shark complement proteins have been isolated and characterized, and these include homologues of C1, C3, and C4. In addition, genes for C3, C4, C5, C8α, C8β, C9, factor B/C2, and factor I have been cloned from shark species. Unfortunately, there is very little information on shark complement receptors and most of the control proteins. Complement of rays and skates has not been studied. With the recent publication of the genome of a chimaera, the elephant shark, Callorhinchus milii, it is hoped that the available sequence information will serve as a blue print for investigators in their efforts to identify and characterize additional complement components of cartilaginous fish and to define their functional role in innate immunity of these lower vertebrates.
