Suppression of local and systemic responses in streptococcal cell wall-induced acute inflammation of the air pouch by cyclosporine A. Comparison with the effects of two anti-inflammatory bis-benzimidazoles.
Injection of streptococcus group A cell wall-derived peptidoglycan polysaccharide into a subcutaneous air pouch causes local outpouring of neutrophils and macrophages and distant hemopoietic proliferation in spleen and bone marrow. Cyclosporine A (CyA) suppressed neutrophil accumulation and all cell lines of hemopoiesis. trans-1,2-Bis(5-amidino-2-benzimidazolyl)ethene (BBE) also interfered with neutrophil exudation, yet reduced only the erythroid component of the hemopoietic process. The ethane analogue of BBE, on the other hand, did not prevent neutrophil emigration, but held down splenic erythropoiesis and myelopoiesis. All three compounds stimulated streptococcus group A cell wall-derived peptidoglycan polysaccharide uptake by pouch macrophages. CyA being the least active, BBE and its ethane analogue also produced a shift of wear-and-tear pigment from large numbers of small splenic macro-phages into small numbers of large macrophages. The pouch model is very useful in the study of anti-inflammatory compounds and has furnished the first evidence of CyA interference with massive neutrophilic infiltration and with hemopoietic signals.
Dieter Geratz
J
J
School of Medicine, Department of Pathology, University of North Carolina, Chapel Hill 27599.
Pryzwansky
K B
KB
Schwab
J H
JH
Anderle
S K
SK
Tidwell
R R
RR
D000818:Animals; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects; D002473:Cell Wall; D016572:Cyclosporine / Q000494:pharmacology*; D005260:Female; D006413:Hematopoietic System / Q000187:drug effects / Q000473:pathology; D006454:Hemoglobins / Q000032:analysis; D006965:Hyperplasia; D007249:Inflammation / Q000382:microbiology* / Q000473:pathology; D007279:Injections, Subcutaneous; D007962:Leukocytes / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013297:Streptococcus pyogenes
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001562:Benzimidazoles; D006454:Hemoglobins; D016572:Cyclosporine