C-type lectins and galectins mediate innate and adaptive immune functions:their roles in the complement activation pathway

In recent years, a 'new' pathway for complement activation mediated by the mannose-binding lectin (MBL) has been described as a key mechanism for the mammalian acute phase response to infection. This complement activation pat hway is initiated by a non-self recognition step: the binding of a humoral C-type lectin [mannose-binding lectin (MBL)] to microbial surfaces bearing 'foreign' carbohydrate determinants. The recognition factor, MBL, is associ ated with a serine protease [MBL-associated serine protease (MASP)] which, upon MBL binding to the microbial ligand, activates the complement componen t C3, leading to either (a) phagocytosis of the opsonized target via the co mplement receptor, or (b) humoral cell killing via assembly of the membrane attack complex. Galectins (formerly known as S-type lectins) modulate acti vity of the complement receptor 3 (CR3), the macrophage membrane receptor f or complement components C3b and iC3b, downstream products of the MBL pathw ay which are covalently bound to 'target' cells. Galectins also mediate mac rophage- and dendrocyte-adhesion to lymphocytes activated by signaling thro ugh another C-type lectin, the L-selectin, leading to immunoglobulin-mediat ed responses. Thus, the functional interplay of MEL, galectins and L-select in in the acute phase response neutralizes the microbial challenge, and lea d to further adaptive immunity. Although the observation of various compone nts of the lectin pathway in different invertebrate species demonstrates th e high conservation and ancient roots of the components of innate immunity, there has previously been no evidence supporting the possibility that the integral lectin-mediated complement activation pathway is present in invert ebrates. We now have evidence for the coexistence of homologs of all the pa thway's key components (MBL, MASP: C3, and galectin) in the protochordate C lavelina picta, suggesting the lectin-mediated pathway of complement activa tion preceded the immunoglobulin pathway in evolution. Therefore, despite b eing 'new' to the textbooks, experimental evidence indicates that this path way is ancient, and has been conserved intact throughout its evolution. (C) 1999 Elsevier Science Ltd. All rights reserved.