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To examine the ability of bacterial lipoproteins from the spirochete Borrelia burgdorferi to cause in vivo tissue injury (arthritis).
Outer surface proteins (OSPs) from B burgdorferi were used in a rat model of antigen-induced allergic arthritis. Intraarticular challenge with recombinant OspA, OspB, and OspC in nonlipidated (peptide) and lipidated forms was performed in the left knee joint; the contralateral joint received buffer as control. Inflammation was monitored by technetium scintigraphy and histology.
Nonlipidated (peptide) OspA, OspB, and OspC did not induce arthritis; the only exception was polymerized OspA, which was tested in preimmunized rats. Lipidated OspA from 2 different strains and lipidated OspC induced severe arthritis, whereas lipidated OspB failed to induce injury. A synthetic analog of the OSP lipid modification, lipopeptide Pam(3)Cys-Ser-Lys(4)-OH, either alone or coupled to bovine serum albumin, also failed to induce injury. Injury did not develop in control groups that were given the appropriate buffers or lipopolysaccharide. This showed that lipidated borrelial OSPs can be potent arthritogens but vary greatly with respect to their injury-inducing potential. The possession of a lipid modification is essential but is not sufficient to render an OSP arthritogenic.
This is the first study to demonstrate that individual lipoproteins from B burgdorferi can induce experimental joint injury in vivo. These results may help elucidate the pathogenesis of
Lyme arthritis and, above all, underline the importance of bacterial lipoproteins as major virulence factors.