Specific ligation of surface alpha-D-galactosyl epitopes markedly affects the quantity of four major proteins secreted by macrophages.
Activated macrophages (M phi s) have terminal alpha-D-galactosyl (alpha D-Gal) residues on their membranes that are not apparent on resting cells. Ligation of these epitopes with Griffonia simplicifolia I-B4 (GSI-B4), a lectin that has specificity for alpha-D-Gal residues, alters selected M phi functions. To explore the mechanism(s) that may be responsible for some of the functional changes, alterations in the secretory pattern of [35S]methionine-labeled proteins were assessed when cells were cultured with or without this ligand. The proteins were identified by Western blots and quantitated. Interestingly, alpha-D-Gal ligation proved to decrease the secretion of some proteins while increasing the secretion of others. Some of the most significant changes were observed in four proteins: fibronectin and transglutaminase were down-regulated by 55 and 66% respectively, while plasminogen activator inhibitor type 2 was increased by 259% and collagenase was increased 1000-fold. These observations show that the emergence of new oligosaccharide epitopes, such as alpha-D-Gal, concomitant with M phi activation may serve to mediate the transduction of signals that cause quantitative changes in the elaboration of diverse M phi products. The biologic significance of the four identified proteins has been well established. Fluctuations in their levels are likely to play a role at sites of chronic inflammation.
Warfel
A H
AH
Department of Medicine, New York University Medical Center, New York 10016.
Zucker-Franklin
D
D
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D000939:Epitopes / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D037102:Lectins / Q000502:physiology; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D003012:Microbial Collagenase / Q000378:metabolism; D015849:Plasminogen Inactivators / Q000378:metabolism; D011503:Transglutaminases / Q000378:metabolism
D001798:Blood Proteins; D000939:Epitopes; D005353:Fibronectins; D037102:Lectins; D015849:Plasminogen Inactivators; D011503:Transglutaminases; D003012:Microbial Collagenase