F icolins are members of the defense collagen family that comprises oligomeric proteins with globular recognition domains able to sense danger signals, such as pathogen-or apoptotic cell-associated molecular patterns, and collagen-like stalks providing the link with immune effectors (1, 2). Ficolins are assembled from homotrimeric subunits comprising a collagen-like triple helix and a lectin-like domain composed of three fibrinogenlike (FBG) 3 domains. Two cysteines at the N-terminal end of the polypeptide chains form interchain disulfide bonds that mediate assembly into higher oligomerization structures (3, 4). In humans, L-and H-ficolins have been characterized in serum whereas Mficolin is mainly expressed by the monocytic cell lineage (5-7). In addition to humans, ficolins have been identified in different mammalian species including rodents and pigs (8, 9), which have two related ficolin genes called A and B and ␣ and , respectively, orthologous to the human L-and M-ficolin genes, respectively (10). To date, H-ficolin has only been identified in humans and it has been reported recently that the mouse and rat homologues of the H-ficolin gene are pseudogenes, which accounts for the absence of the corresponding protein in rodents (10). Like mannan-binding lectin (MBL), ficolins are able to activate the lectin complement pathway in response to recognition of neutral carbohydrates and N-acetyl groups on pathogens and damaged cells. This results from the ability of MBL and ficolins to associate with and trigger activation of MBL-associated serine protease (MASP)-2. Activated MASP-2 cleaves the complement proteins C2 and C4, thereby triggering the complement cascade (11-13). Three other MBL/ficolins-associated proteins have been described, the MASP-1 and MASP-3 proteases (14, 15) and a truncated form of MASP-2 called MAp19 (19-kDa MBL-associated protein) or sMAp (16,17). MASP-3 has no known physiological substrates whereas MASP-1 cleaves with a low efficiency a few protein substrates, among which are fibrinogen and coagulation factor XIII (18). It has been proposed recently that MASP-1 might contribute to the activation of the lectin pathway, but this issue is still controversial (19,20). Complement activation results in opsonization of microbes and apoptotic cells with C3-derived fragments, thus promoting their clearance through interaction with C3 receptors on The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.1 This work was supported by the Commissariat à l'Energie Atomique, the Centre National de la Recherche Scientifique, the Université Joseph Fourier (Grenoble, France).
