Role of monocyte fucose-receptors in T-cell fibronectin activity.
T-cell fibronectin (FN) is a lymphokine produced by antigen- and mitogen-activated T cells that agglutinates human monocytes at femtomolar concentrations. This extreme degree of activity derives from co-operative interactions between multiple FN domains and multiple monocyte integrin protein receptors. T-cell FN, like other FN, is a glycoprotein. The role interactions between T-cell FN carbohydrate and lectin-like monocyte surface receptors play in mediating T-cell FN activity was studied by determining the ability of monosaccharides to inhibit T-cell FN activity. L-Fucose and L-rhamnose significantly inhibited T-cell FN-mediated monocyte agglutination at concentrations as low as 0.01 mM; D-glucose, D- or L-galactose, D- or L-mannose and D-fucose were not inhibitory at 10-100 mM. This inhibition appeared to be due to interference with the binding of T-cell FN fucose residues to monocyte fucose receptors since: (i) treatment of T-cell FN with alpha-L-fucosidase abolished its agglutinating activity for human monocytes, while treatment with beta-D-galactosidase or with alpha-L-fucosidase in the presence of L-fucose had no effect; (ii) treatment of monocytes with alpha-L-fucosidase did not affect their response to T-cell FN; and (iii) L-fucose or L-rhamnose did not alter the expression of monocyte integrin FN receptors under conditions where T-cell FN-mediated monocyte agglutination was completely inhibited. In vivo, 1 mumol intracutaneous L-fucose inhibited expression of delayed hypersensitivity by 30% (P much less than 0.001); similar doses of L-rhamnose inhibited responses by 10% (P less than 0.02). These data implicate a fucose receptor in monocyte response to T-cell FN, and suggest that T-cell FN is only one of the mediators involved in initiating delayed hypersensitivity reactions in vivo.
Donson
J
J
Department of Experimental Pathology, New York Medical College, Valhalla 10595.
Mandy
K
K
Feng
Z H
ZH
Mandy
S
S
Brown
E J
EJ
Godfrey
H P
HP
D002449:Cell Aggregation / Q000187:drug effects; D002478:Cells, Cultured; D005353:Fibronectins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D005643:Fucose / Q000378:metabolism; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D009000:Monocytes / Q000502:physiology*; D009005:Monosaccharides / Q000494:pharmacology; D011975:Receptors, Mitogen / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*
D005353:Fibronectins; D009005:Monosaccharides; D011975:Receptors, Mitogen; D005643:Fucose