ABSTRACT
The synthesis and secretion of proteins, especially interleukin 1 (IL-1), by mononuclear cells from patients with rheumatoid arthritis (RA) in response to heat-aggregated IgG (HAGG) has been investigated. Mononuclear cells were labeled with 35S-methionine during 1 hr of HAGG stimulation, and the intracellular and extracellular protein content was measured and compared by fluorography. HAGG dramatically accelerated protein release into the medium. This was observed in both normal and RA mononuclear cells but was much more marked with the latter. The phenomenon was correlated with the release of a IL-1 activity measurable in the thymocyte proliferation assay with a more pronounced labeling in the extracellular medium of a 14-kDa band not detectable in the intracellular pattern. Partially purified proteins between 14-20 kDa recovered by transblotting also stimulated thymocyte proliferation. These results therefore suggest a particular sensitivity of RA mononuclear cells to HAGG, resulting in a very rapid de novo synthesis and an accelerated secretion rate of IL-1.
Subject(s)
Arthritis, Rheumatoid/immunology , Immunoglobulins/physiology , Leukocytes, Mononuclear/metabolism , Protein Biosynthesis , Adult , Arthritis, Rheumatoid/metabolism , Female , Hot Temperature , Humans , Interleukin-1/biosynthesis , Interleukin-1/isolation & purification , Intracellular Fluid/metabolism , Kinetics , Macromolecular Substances , Male , Middle Aged , Molecular WeightABSTRACT
The leukocyte adherence inhibition (LAI) test in arthritis is a model of cooperation between monocytes, T cells and polymorphonuclear cells (PMN). Mononuclear cells (MNC) from patients with rheumatoid arthritis in contact with aggregated IgG release within 60 min in the test tube a supernatant capable of inhibiting the adherence of PMN to glass (LAI activity). By protein labeling, fractionation and electroblotting, we showed that the supernatant LAI activity was located in the 14-20 kDa region of the gel and was actively secreted upon MNC stimulation. Under negative conditions, the factors with LAI activity were able to constitute larger complexes and their charge was heterogeneous. Their relationship to interleukin-1 (IL-1) is discussed, since the supernatant gave a positive response in the thymocyte proliferation assay; small amounts of IL-1 had the capacity to inhibit PMN adhesiveness and anti-IL-1 blocked this activity.
