Effect of phospholipase A2 inhibitors on mouse T lymphocytes. I. Phospholipase A2 inhibitors exert similar immunological activities as glycosylation inhibiting factor.
Since our previous experiments suggested that glycosylation-inhibiting factor (GIF) is a phosphorylated derivative of a phospholipase inhibitory protein, we determined whether other well-known phospholipase inhibitors may have similar biological activities. The results showed that phospholipase A2 (PLA2) inhibitors, such as recombinant human lipocortin I and ONO-RS-082, could switch T cell hybridoma 12H5 cells from the formation of glycosylated IgE-binding factors (IgE-BF) to the formation of unglycosylated IgE-BF, whereas neomycin, a phospholipase C inhibitor, failed to affect the nature of IgE-BF formed by the cells. The minimum concentrations of lipocortin I and ONO-RS-082 required for switching the 12H5 cells to the formation of unglycosylated IgE-BF were comparable to or less than IC50 of the inhibitors for PLA2. The ability of partially purified GIF to switch the 12H5 cells to the formation of unglycosylated IgE-BF was markedly enhanced by treatment of the preparation with alkaline phosphatase. It was also found that lipocortin I and ONO-RS-082, but not neomycin, facilitated the generation of GIF-producing T cells. When spleen cells of ovalbumin (OVA)-primed BDF1 mice were stimulated with homologous antigen and the activated T cells were propagated by recombinant IL-2 in the presence of GIF, lipocortin I, or ONO-RS-082, T cells obtained in the cultures constitutively produced their own GIF. Antigenic stimulation of the T cells induced the formation of unglycosylated IgE-BF and GIF with an affinity for OVA.(ABSTRACT TRUNCATED AT 250 WORDS)
Ohno
H
H
Department of Medicine, Johns Hopkins University, School of Medicine, Good Samaritan Hospital, Baltimore, MD 21239.
Iwata
M
M
Nakamura
T
T
Ishizaka
K
K
D062365:Aminobenzoates / Q000494:pharmacology; D000818:Animals; D017302:Annexins; D002135:Calcium-Binding Proteins / Q000494:pharmacology; D002723:Chlorobenzoates; D002934:Cinnamates / Q000494:pharmacology; D005260:Female; D006031:Glycosylation; D066298:In Vitro Techniques; D008222:Lymphokines / Q000494:pharmacology*; D051379:Mice; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D029584:Prostatic Secretory Proteins; D013491:Suppressor Factors, Immunologic / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D062367:ortho-Aminobenzoates
D062365:Aminobenzoates; D017302:Annexins; D002135:Calcium-Binding Proteins; D002723:Chlorobenzoates; D002934:Cinnamates; D008222:Lymphokines; D029584:Prostatic Secretory Proteins; D013491:Suppressor Factors, Immunologic; C043076:beta-microseminoprotein; C013059:immunoglobulin-binding factors; D062367:ortho-Aminobenzoates; C060048:2-(4-amylcinnamoyl)amino-4-chlorobenzoic acid; D010741:Phospholipases A; D054467:Phospholipases A2