This study proposes to examine if B. burgdorferi lipoproteins could play a direct role in inducing the synovitis of Lyme arthritis. The initial research phase will use the well characterized rat synovial cell culture as a source of purified synovium. Synovial cell cultures treated with recombinant lipoproteins (OspA, OspC and lipopeptides) will be examined for proliferation. Further, known proinflammatory products expressed by activated synovial cells: cytokines, nitric oxide and metalloproteases, will be assayed. These factors could enhance the inflammation and tissue damage associated with Lyme arthritis. Based on preliminary data, costimulation with host factors enhanced the lipoprotein responses, therefore, synergy between proinflammatory cytokines (e.g., INFgamma, IL1beta, TNFalpha) will be examined. The results of the in vitro study will be applied to the rat and mouse animal model for Lyme arthritis. Combinations of lipoprotein and cytokines determined to activate cultured synovial cell will be injected into rat (neonate LEW/N) and mice (C3H and C57/b6) knee joints and their effects assessed. The ability of lipoprotein to induce proliferation of synovium would strongly a support direct role of B. burgdorferi lipoproteins in disease pathology.
