Monocyte scintigraphy in rheumatoid arthritis: the dynamics of monocyte migration in immune-mediated inflammatory disease.
BACKGROUND
Macrophages are principal drivers of synovial inflammation in rheumatoid arthritis (RA), a prototype immune-mediated inflammatory disease. Conceivably, synovial macrophages are continuously replaced by circulating monocytes in RA. Animal studies from the 1960s suggested that macrophage replacement by monocytes is a slow process in chronic inflammatory lesions. Translation of these data into the human condition has been hampered by the lack of available techniques to analyze monocyte migration in man.


RESULTS
We developed a technique that enabled us to analyze the migration of labelled autologous monocytes in RA patients using single photon emission computer tomography (SPECT). We isolated CD14+ monocytes by CliniMACS in 8 patients and labeled these with technetium-99m (99mTc-HMPAO). Monocytes were re-infused into the same patient. Using SPECT we calculated that a very small but specific fraction of 3.4 x 10(-3) (0.95-5.1 x 10(-3)) % of re-infused monocytes migrated to the inflamed joints, being detectable within one hour after re-infusion.


CONCLUSIONS
The results indicate monocytes migrate continuously into the inflamed synovial tissue of RA patients, but at a slow macrophage-replacement rate. This suggests that the rapid decrease in synovial macrophages that occurs after antirheumatic treatment might rather be explained by an alteration in macrophage retention than in monocyte influx and that RA might be particularly sensitive to treatments targeting inflammatory cell retention.
Thurlings
Rogier M
RM
Department of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, Noord Holland, The Netherlands.
Wijbrandts
Carla A
CA
Bennink
Roelof J
RJ
Dohmen
Serge E
SE
Voermans
Carlijn
C
Wouters
Diana
D
Izmailova
Elena S
ES
Gerlag
Danielle M
DM
van Eck-Smit
Berthe L F
BL
Tak
Paul P
PP
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology*; D002465:Cell Movement; D005260:Female; D006801:Humans; D007107:Immune System / Q000502:physiology*; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D011877:Radionuclide Imaging / Q000379:methods*; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
D018950:Lipopolysaccharide Receptors