Intracellular signaling involved in macrophage adhesion and FBGC formation as mediated by ligand-substrate interaction.
Fibronectin and RGD- and/or PHSRN-containing oligopeptides were preadsorbed onto physicochemically distinct substrata: polyethyleneglycol-based networks or tissue culture polystyrene (TCPS). The role of selected signaling kinases (namely protein tyrosine kinases, protein serine/threonine kinases, PI3-kinase, Src, and MAPK) in the adhesion of human primary blood-derived macrophages and the formation of foreign-body giant cells (FBGC) on these modified substrata was investigated. The involvement of individual intracellular signaling molecules in mediating macrophage adhesion dynamically varied with the culture time, substrate, and ligand. For example, fibronectin on TCPS or networks involved similar signaling events for macrophage adhesion; however, fibronectin and G(3)RGDG(6)PHSRNG, but not peptides with other RGD and/or PHSRN orientations, mediated similar signaling events for macrophage adhesion on TCPS but mediated different signaling events on networks. Depending on the substrate, a specific molecule (i.e., Src, protein kinase C) within the protein tyrosine kinase or protein serine/threonine kinase family was either an antagonist or agonist in mediating FBGC formation.
Kao
Weiyuan John
WJ
School of Pharmacy, University of Wisconsin-Madison, Madison, WI 53705, USA. wjkao@pharmacy.wisc.edu
Liu
Yiping
Y
D000327:Adsorption; D000730:Androstadienes / Q000494:pharmacology; D002448:Cell Adhesion / Q000502:physiology*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D015743:Giant Cells, Foreign-Body / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008024:Ligands; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000378:metabolism*; D011137:Polystyrenes / Q000378:metabolism*; D011487:Protein Conformation; D015398:Signal Transduction / Q000502:physiology*; D013499:Surface Properties; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D005353:Fibronectins; D016023:Integrins; D008024:Ligands; D010446:Peptide Fragments; D010636:Phenols; D011137:Polystyrenes; D011092:Polyethylene Glycols; C062898:lavendustin A; D066246:ErbB Receptors; D000077191:Wortmannin