Suppression of human interferon-gamma production by a 17 amino acid peptide homologous to the transmembrane envelope protein of retroviruses: evidence for a primary role played by monocytes.
CKS-17, a synthetic amino acid peptide homologous to a highly conserved region of retroviral transmembrane protein exerts a suppressive action on staphylococcal enterotoxin A (SEA)-induced the production of IFN-gamma by human peripheral blood mononuclear cells (PBMC) (Ogasawara et al., J. Immunol. 141, 615, 1988). This action has been shown in the present study to be preceded by dramatic clustering of PBMC. Clusters appear within 3 hr of exposure of PBMC to CKS-17; they are dose dependent, inhibited by cycloheximide, and require a temperature of 37 degrees C. The cells in the clusters are predominantly monocytes. Although it has been previously shown that CKS-17 inhibits monocyte-mediated killing by inactivating IL-1 (Kleinerman et al., J. Immunol. 139, 2329, 1987) and production of IL-2 by murine thymoma cells treated with IL-1 (Gottlieb et al., J. Immunol. 142, 4321, 1989), in the present study we show that IL-1 does not prevent clustering of PBMC by CKS-17. Using CKS-17 and highly purified monocytes or lymphocytes, profound alterations occur only with monocytes, as revealed by light or electron microscopy. SEA- or staphylococcal enterotoxin B-induced production of IFN-gamma is inhibited when highly purified monocytes pretreated with CKS-17 are cocultured with highly purified T lymphocytes. Thus, CKS-17 induces dramatic clustering of cells apparently by inducing alterations of monocytes but not lymphocytes, suggesting that CKS-17 may interfere with the capacity of monocytes to facilitate production of IFN-gamma by T lymphocytes.
Haraguchi
S
S
Department of Pediatrics, All Children's Hospital, University of South Florida, St. Petersburg 33701.
Liu
W T
WT
Cianciolo
G J
GJ
Good
R A
RA
Day
N K
NK
D000595:Amino Acid Sequence; D002450:Cell Communication / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000648:ultrastructure; D010455:Peptides / Q000494:pharmacology*; D012190:Retroviridae / Q000737:chemistry*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014759:Viral Envelope Proteins / Q000494:pharmacology*
D010455:Peptides; D014759:Viral Envelope Proteins; D007371:Interferon-gamma