Prostaglandins, Cellular Immunity and Rheumatic Disease

Goldyne, Marc

Abstract

The specific aims of this project are: 1) To further characterize endogenous prostaglandin (PG) production among normal human peripheral blood mononuclear cells (PBMC) that respectively produce or fail to produce leukocyte inhibitory factor (LIF) in response to collagen. 2) To identify subpopulations of monocytes and T cells involved in PG production among normal PBMC. 3) To identify pathways involved in generating any changes in PG production among normal monocytes and T cells following exposure to collagen. 4) To characterize, among normal PBMC, possible relationships between endogenous PG production and the generation of LIF. 5) To evaluate similar aspects of PG metabolism among PBMC from patients with rheumatoid arthritis in response to collagen. The long term objective is to identify possible immunomodulatory roles of endogenously synthesized PGs or possibly other arachidonic acid metabolites in cellular immune responses. The increased frequency of immunoreactivity to collagen among patients with rheumatoid arthritis and the association of alterations in PG synthesis we have recently found among immunocompetent cells in response to collagen suggests the possibility of a connection between PGs and collagen reactivity in normal individuals as well as in patients wit rheumatoid arthritis. PG radioimmunoassays, 14C-arachidonic acid labeling studies, isolation of monocyte or T cell subsets using discontinuous density gradients, and monoclonal antibodies that recognize functionally distinct subsets of monocytes or T cells will all be used to evaluate the role of endogenously synthesized PGs in modulating cellular immune response and to define the specific immunocompetent cells that can influence antigen related PG metabolism. Using a model of cellular immune response that may be pertinent to rheumatoid arthritis may provide insight as to whether PG dependent immunomodulation is altered in patients with rheumatoid arthritis.