SIALYL LEWIS(X) EPITOPES DO NOT OCCUR ON ACUTE-PHASE PROTEINS IN MICE- RELATIONSHIP TO THE ABSENCE OF ALPHA-3-FUCOSYL-TRANSFERASE IN THE LIVER

Mice are frequently used in models for the study of immunological proc esses related to inflammation. Since it is known that the degree of fu cosylation of human acute phase proteins (APPs) is altered as a conseq uence of an inflammatory response, we have undertaken this study to ga in more insight into the fucosylation of acute phase proteins as it oc curs in mouse liver. Mice carrying the cluster of the three genes enco ding human alpha 1-acid glycoprotein (AGP), one of the well known APPs , were used and the fucosylation of AGP was assessed. A complete absen ce of fucosylation on the transgenic human AGP was found, which is in sharp contrast to AGP in human serum, of which a major proportion is n ormally alpha 3-fucosylated. Remarkably, a large proportion of mouse A GP did contain fucose residues. Fucosylation was also detected on anot her APP, mouse protease inhibitor (PI). alpha 3-Fucosylation of the tr ansgenic human AGP can be achieved in vitro, using an alpha 3/4-fucosy ltransferase (alpha 3/4-FucT) isolated from human milk, showing that t he glycoprotein is not intrinsically resistant to fucosylation. Upon s ubsequent measurement of the activities of the possible fucosyltransfe rases present in liver membranes of parent and transgenic mice, only a n N-linked-core alpha 6-FucT and no alpha 2-, alpha 3- or alpha 4-FucT activity was detected. This indicates that fucose residues found on t he mouse serum proteins AGP and PI, which are synthesized in the liver , are most probably in alpha 6-linkage to the core chitobiosyl unit. I nterestingly, both alpha 6- and alpha 3-FucT activity was detectable i n human liver membranes. None of the above mentioned findings were inf luenced by the induction of an acute phase response by administration of bacterial lipopolysaccharide. This study shows that: (a) alpha 6-Fu cT is probably a protein specific-glycosyltransferase, since mouse AGP , but not human AGP, may be used as an acceptor; (b) in contrast to hu man liver, mouse liver does not express any alpha 3-FucT-activity, the reby making the mouse incapable of producing the Sialyl Lewis(x) epito pe on APPs, which is an important part of the inflammatory reaction in humans. This last finding indicates that the mouse is not suitable as a model for the study of those phenomena related to inflammation in h umans, in which glycosylation of acute phase proteins could play a sig nificant role.