Streptococcal cell wall-induced systemic disease. Beneficial effects of trans-bis(5-amidino-2-benzimidazolyl)ethene, a novel, macrophage- directed anti-inflammatory agent [published erratum appears in Am J Pathol 1992 Jan;140(1):following Table of Contents]

• Published in: The American journal of pathology Vol. 139; no. 4; pp. 921 - 931
• Main Authors: Geratz, JD, Tidwell, RR, Lombardy, RJ, Schwab, JH, Anderle, SK, Pryzwansky, KB
• Format: Journal Article
• Language: English
• Published: United States ASIP 01-10-1991
• Subjects: Animals; Benzimidazoles - therapeutic use; Cell Membrane - metabolism; Cell Membrane - ultrastructure; Female; Granulomatous Disease, Chronic - drug therapy; Granulomatous Disease, Chronic - pathology; Inflammation - chemically induced; Inflammation - drug therapy; Inflammation - pathology; Liver - drug effects; Liver - pathology; Liver - ultrastructure; Macrophages - drug effects; Macrophages - pathology; Macrophages - ultrastructure; Microscopy, Electron; Peptidoglycan; Polysaccharides; Rats; Rats, Inbred Lew; Spleen - drug effects; Spleen - pathology; Spleen - ultrastructure; Streptococcus - metabolism; Streptococcus - ultrastructure; Structure-Activity Relationship
• ISSN: 0002-9440; 1525-2191

Previously bis(5-amidino-2-benzimidazolyl)methane (BABIM) was identified as a strong inhibitor of the multisystem inflammatory disease induced in Lewis rats by injection of streptococcus group A cell wall-derived peptidoglycan polysaccharide (PG-APS). A BABIM derivative, trans-bis(5-amidino-2-benzimidazolyl)ethene (BBE), has attracted attention because of striking qualitative and quantitative differences in its activities when compared with the parent compound. BBE could control destructive tibial osteitis and necrotizing granulomatous splenitis and hepatitis, regardless if given in a preventive or curative mode. The compound had little effect on synovitis, however. BABIM, on the other hand, was active against synovitis and osteitis, but not against splenic granuloma formation. To be effective, it needed to be applied in a preventive mode. BBE caused a characteristic enlargement of PG-APS-laden splenic and hepatic macrophages suggesting that those cells represent targets of the inhibitor. BBE may be a powerful tool for the study of granulomatous lesions.