We investigated the in vivo role of phagocytic synovial lining cells (
SLC) in the onset of experimental arthritis by depleting phagocytic SL
C prior to arthritis induction. Phagocytic SLC were depleted by a sing
le intra-articular injection of liposomes encapsulating the drug dichl
oromethylene diphosphonate (CL2MDP). Seven days after injection optima
l depletion was observed and this time point was chosen for induction
of arthritis in SLC depleted joints. Joint swelling was highly reduced
after elicitation with either zymosan, immune complexes or antigen, a
s compared to observations in normal non-depleted joints. In addition
cellular infiltration was markedly reduced. Further study in the immun
e complex mediated arthritis revealed that reduced cell influx in SLC
depleted knee joints was correlated to lowered chemotactic activity an
d IL-1 levels as measured in washouts of joint tissues. This indicates
that IL-1 driven chemotactic factors might be involved. Furthermore r
educed cell influx was also correlated to significantly diminished los
s of S-35-prelabeled PG from the cartilage. Out data indicate that SLC
are directly involved in the onset of joint inflammation.