A NOVEL HUMAN SERUM LECTIN WITH COLLAGEN-LIKE AND FIBRINOGEN-LIKE DOMAINS THAT FUNCTIONS AS AN OPSONIN

Collectins are C-type animal lectins with both collagenous and carbohy drate recognition domains and are involved in the first line host defe nse against pathogens, We report here a novel Ca2+-dependent and GlcNA c-binding lectin consisting of subunits of 35 kDa (P35) with a collage n-like sequence, When P35 is isolated from human serum, it forms a hom opolymer by means of intermolecular disulfide bonding, as is the case with collectins, P35 cDNA was cloned from a human liver cDNA library, and the deduced amino acid sequence of 313 residues revealed that the mature form of P35 consists mainly of collagen- and fibrinogen-like do mains, The latter contained two potential Ca2+-binding sites that may be involved in carbohydrate binding, The overall sequence of P35 was h ighly homologous to porcine ficolins alpha and beta. Northern blots of various human tissues showed that the major product of the 1.3-kiloba se-long P35 transcript is expressed in liver, P35 enhanced phagocytosi s of Salmonella typhimurium by neutrophils, suggesting an opsonic effe ct via the collagen region, P35 was found to bind to GlcNAc-conjugated bovine serum albumin, a neoglycoprotein, as web as to neoglycolipids containing complex-type oligosaccharides derived from glycoproteins, s uggesting that P35 recognizes GlcNAc residues such as those found in m icrobial glycoconjugates and complex-type oligosaccharides. Therefore, P35 represents a new type of GlcNAc-binding lectin with structural an d functional similarities to collectins involved in innate immunity.