Abstract
Introduction: Metal on Metal articulations produce Cobalt Chromium nanoparticles (CoCrNP) which seems to affect the adaptive immune system, as evident from the perivascular infiltrate of lymphocytes & plasma cells found around some implants, and the reduced CD8+ count described with hip resurfacing. We therefore analyzed effects of CoCrNP on Dendritic Cells, T cells & B cells.
Methods: CoCrNP were produced by repetitive short spark discharges between electrodes of prosthetic CoCr alloy. Electron micrography & BET both confirmed nanoparticle size.
-
Dendritic Cells were cultured from mouse bone marrow and incubated with CoCrNP of varying concentrations, for 24hrs, or lipopolysaccharide as a positive control. Activation status was then characterized by CD40 expression on FACS analysis.
-
Cells from mouse lymph nodes were incubated with CoCrNP in varying concentrations. At 48hrs, Propidium Iodide (PI) was added & % PI+ve determined on FACS analysis.
-
Cells from mouse lymph nodes were cultured in medium without phenol red and incubated with ∝CD3, ∝CD3 + CoCrNP, ∝CD3 + ∝CD28 or ∝CD3 + ∝CD28 + CoCrNP. At 48hrs, Almar Blue was added & difference in light absorbance at 570nm & 600nm was then used to determine T cell proliferation at 72hrs.
-
Cells from lymph nodes of an MD4 mouse (only able to mount a b cell response to Hen egg Lysozyme (HEL)) were incubated with CoCrNP, HEL (positive control) or CoCrNP + HEL. B cell regulation at 48hrs was characterized by CD40 and CD86 expression on FACS analysis.
Results: CoCrNP did not significantly increase CD 40 expression on DCs or Cd 40/ Cd 86 expression on B cells. At subletal concentrations, CoCrNP inhibited ∝CD3 & ∝CD28 dependent T-cell proliferation.
Discussion: CoCrNP reduces both signal 1 & signal 2 dependent T cell proliferation, which may explain the observed reduction in CD 8+ count with hip resurfacing.
Correspondence should be addressed to Mr John Hodgkinson, BHS, c/o BOA, The Royal College of Surgeons, 35–43 Lincoln’s Inn Fields, London WC2A 3PE.
