Sequential events in the pathogenesis of streptococcal cell wall-induced arthritis and their modulation by bis(5-amidino-2-benzimidazolyl)methane (BABIM).
This report builds on the authors' earlier discovery of bis(5-amidino-2-benzimidazolyl)methane (BABIM) as a strong suppressive agent for streptococcal cell wall fragment-induced arthritis in the Lewis rat. As a synthetic inhibitor of trypsinlike proteases, BABIM opens up a new route to the control of inflammatory joint disease. To gain a deeper insight into the function of the compound, the authors have now studied its influence on the sequential development of the joint changes and the associated lesions in spleen and liver. Bis(5-amidino-2-benzimidazolyl)methane is shown to block acute synovitis, to retard and reduce granuloma formation in spleen and liver, to decrease neutrophilic leukocytosis, and to diminish hemopoietic hyperplasia in the bone, and thus also to mitigate the distinctive osteoclastic and chondroclastic events. The compound does not interfere with the splenic immune response, the temporary rise in hepatocytic mitotic activity, or the organ deposition of streptococcal cell walls.
Geratz
J D
JD
Department of Pathology, University of North Carolina, Chapel Hill 27599.
Tidwell
R R
RR
Schwab
J H
JH
Anderle
S K
SK
Pryzwansky
K B
KB
D000818:Animals; D001168:Arthritis / Q000382:microbiology / Q000473:pathology*; D001562:Benzimidazoles / Q000494:pharmacology*; D002473:Cell Wall; D007958:Leukocyte Count; D008099:Liver / Q000473:pathology; D010457:Peptidoglycan / Q000633:toxicity; D011135:Polysaccharides, Bacterial / Q000633:toxicity; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000473:pathology; D013291:Streptococcus / Q000472:pathogenicity*; D013583:Synovial Membrane / Q000473:pathology; D013997:Time Factors
D001562:Benzimidazoles; D010457:Peptidoglycan; D011135:Polysaccharides, Bacterial; D011480:Protease Inhibitors; C025426:bis(5-amidino-2-benzimidazolyl)methane