The effect of human bone matrix extracts on the biosynthesis of macromolecules by human mononuclear cells in culture.
In chronic rheumatoid arthritis, mononuclear cells (MC) accumulate in the subchondral bone and form a prominent part of both destructive lesions and repair reactions. A fraction from human bone matrix extracts (BME) stimulated glycosaminoglycan (gag) and glycoprotein synthesis by fibroblastic cells but its effects on MC metabolism had not been studied. A method was established for the study of incorporation of radioactive precursors into total protein, IgG and gag synthesized and secreted by peripheral blood MC cultured in microwells in the presence or absence of Concanavalin A (ConA). Relatively low concentrations of BME suppressed spontaneous synthesis of radioactive IgG (protein A bound) and TCA precipitable protein but had little effect on gag synthesis. In general, stimulation of the cultures with ConA overcame the inhibitory effects on protein synthesis by the BME. A large stimulation of gag synthesis induced by ConA was not affected by BME. The interactions between the BME and the stimulatory effect of ConA on DNA synthesis were studied in detail and were found to be complex, not immunologically specific and appeared to be due to binding of lectin by the carbohydrate moieties of the glycoproteins in the BME. On the basis of a model of the lectin-BME interaction, the hypothesis is postulated that the carbohydrate moieties of subchondral bone glycoproteins may have the capacity to act as a solid state "trap" for certain circulating antigens which may then also interact with surface glycoproteins of the MC accumulating in the subchondral bone. The physiological role of gag synthesis by MC is not known.
D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000503:physiopathology*; D001857:Bone Matrix / Q000276:immunology / Q000502:physiology*; D002478:Cells, Cultured; D011232:Chemical Precipitation; D003208:Concanavalin A / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D006023:Glycoproteins / Q000276:immunology; D006025:Glycosaminoglycans / Q000096:biosynthesis; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007700:Kinetics; D008214:Lymphocytes / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D014176:Protein Biosynthesis
D006023:Glycoproteins; D006025:Glycosaminoglycans; D007074:Immunoglobulin G; D003208:Concanavalin A; D004247:DNA