Preferential suppression of delayed-type hypersensitivity by L-156,602, a C5a receptor antagonist.
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.
Department of Agricultural Chemistry, University of Tokyo, Japan.
R F
RF
Tsuji
M
M
Uramoto
H
H
Koshino
N M
NM
Tsuji
J
J
Magae
K
K
Nagai
M
M
Yamasaki
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D002004:Brucella Vaccine / Q000494:pharmacology; D002003:Brucella abortus / Q000276:immunology; D015936:Complement C5a / Q000037:antagonists & inhibitors*; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D006968:Hypersensitivity, Delayed / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010456:Peptides, Cyclic / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology*; D012756:Sheep; D013302:Streptomyces / Q000737:chemistry / Q000145:classification / Q000378:metabolism
D000276:Adjuvants, Immunologic; D002004:Brucella Vaccine; D010456:Peptides, Cyclic; C051485:PD 124966; D015936:Complement C5a