Bacterial cell wall polymers (peptidoglycan-polysaccharide) cause reactivation of arthritis.
Intraperitoneal (i.p.) injection of peptidoglycan-polysaccharide derived from group A streptococci (PG-APS) causes chronic arthritis with spontaneous remissions and exacerbations. We hypothesized that, following i.p. injection, PG-APS released from hepatic stores mediated spontaneous recurrences of arthritis. We tested whether transplanted livers with large amounts of PG-APS were able to reactivate quiescent arthritis. Saline-loaded (group 1) or PG-APS-loaded (group 2) livers were transplanted into rats which had been injected intra-articularly 10 days earlier with PG-APS in one joint and saline in the other. A comparison was made with the arthritis that occurred in rats injected i.p. with PG-APS which did not receive transplants (group 3). Arthritis was monitored by serial measurement of joint diameters. Transplantation of saline-loaded livers (group 1) caused no reactivation of arthritis. However, transplantation of PG-APS-loaded livers (group 2) reactivated arthritis (P < 0.0001). Injection of PG-APS i.p. (group 3) induced the most-severe arthritis. PG-APS levels in plasma decreased with time, and PG-APS accumulated in the spleen in groups 2 and 3. Plasma and hepatic levels of PG-APS in rats injected i.p. with PG-APS were greater than levels in rats transplanted with PG-APS-loaded livers, which in turn were greater than levels in rats with saline-loaded livers. Plasma tumor necrosis factor did not correlate with recurrence of arthritis. Transplantation with PG-APS-loaded livers induced reactivation of arthritis in preinjured joints. The extent of arthritis was proportional to hepatic PG-APS content. Reactivation of arthritis may be mediated by slow release of liver-sequestered PG-APS or cytokines (not tumor necrosis factor) released by the liver.
Lichtman
S N
SN
Department of Pediatrics, University of North Carolina, Chapel Hill 27599-7220.
Bachmann
S
S
Munoz
S R
SR
Schwab
J H
JH
Bender
D E
DE
Sartor
R B
RB
Lemasters
J J
JJ
D000818:Animals; D001168:Arthritis / Q000209:etiology*; D002473:Cell Wall / Q000737:chemistry; D006520:Hepatitis, Animal / Q000209:etiology; D008099:Liver / Q000378:metabolism; D008297:Male; D010457:Peptidoglycan / Q000378:metabolism / Q000633:toxicity*; D011108:Polymers / Q000378:metabolism / Q000633:toxicity; D011135:Polysaccharides, Bacterial / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D011917:Rats, Inbred Lew; D012008:Recurrence; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D010457:Peptidoglycan; D011108:Polymers; D011135:Polysaccharides, Bacterial; D014409:Tumor Necrosis Factor-alpha