Preferential Suppression of Delayed-type Hypersensitivity by L-156,602, a C5a Receptor Antagonist

• Published in: Bioscience, biotechnology, and biochemistry Vol. 56; no. 10; pp. 1686 - 1689
• Main Authors: Tsuji, Ryohei F., Uramoto, Masakazu, Koshino, Hiroyuki, Tsuji, Noriko M., Magae, Junji, Nagai, Kazuo, Yamasaki, Makari
• Format: Journal Article
• Language: English
• Published: Tokyo Taylor & Francis 1992; Japan Society for Bioscience Biotechnology and Agrochemistry; Oxford University Press
• Subjects: Adjuvants, Immunologic - pharmacology; Animals; Antibody Formation - drug effects; Biological and medical sciences; Biotechnology; Brucella abortus - immunology; Brucella Vaccine - pharmacology; Complement C5a - antagonists & inhibitors; Erythrocytes - drug effects; Female; Hypersensitivity, Delayed - drug therapy; Immunomodulators; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Peptides, Cyclic - biosynthesis; Peptides, Cyclic - isolation & purification; Peptides, Cyclic - pharmacology; Pharmacology. Drug treatments; Sheep; Streptomyces - chemistry; Streptomyces - classification; Streptomyces - metabolism; Complement C5; Immunopathology; Streptomycetaceae; Rodentia; Streptomyces; Delayed hypersensitivity; Actinomycetales; Vertebrata; Chemotherapy; Mammalia; Treatment; Microbial origin; Mouse; Animal; Bacteria; Actinomycetes; Antagonist; Biological receptor
• ISSN: 0916-8451; 1347-6947
• DOI: 10.1271/bbb.56.1686

In the course of our screening for in vivo immunomodulating substances in which sheep red blood cells (SRBC) and heat-killed Brucella abortus cells (thymus dependent and independent antigens, respectively) for antibody production assays, and trinitrobenzene sulfonic acid (TNBS) for delayed-type hypersensitivity (DTH) assay were adopted as antigens, we detected a DTH-specific suppressive activity. The producing organism was isolated from a soil sample collected in Ushiku City, Ibaraki, Japan and identified with Streptomyces sp. A1502 (FERM P-12448). The active component was identified with L-156,602, a C5a receptor antagonist. L-156,602 suppressed both TNBS-induced and TNP-SRBC-induced DTH while it enhanced antibody production against SRBC, Brucella abortus, and TNP-SRBC. L-156,602 significantly suppressed DTH induced by direct injection of type 1 helper T cells and its relevant antigen into hind-footpads, indicating that the efferent phase of DTH was affected by L-156,602. The results demonstrated that L-156,602 preferentially suppressed the DTH response.