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Interaction of Human Cells with Prostaglandins and Cyclic AMP Modulators

I. Effects on Complement-Mediated Lysis and Antibody-Dependent Cell-Mediated Cytolysis of Herpes Simplex Virus-Infected Human Fibroblasts¹

From the Department of Pathology, Box 3712, Duke University Medical Center, Durham, North Carolina 27710

Abstract

The release of prostaglandins (PG) has been incriminated in exacerbations of latent herpes simplex virus (HSV) infections in humans, but the mechanism(s) by which PG could precipitate a recurrence has not been adequately explored. In this study we determined the effect of PG-A₁, B₁, E₁, E₂, F₂, and other cAMP elevating agents had on complement (C)mediated lysis and antibody-dependent cell-mediated cytolysis (ADCC) of HSV-infected human fibroblasts (HuF). C-lysis was not inhibited by PG, phosphodiesterase inhibitors, or dibutyryl-cAMP regardless of the concentrations of reagent, human antiHSV, or C that was incubated with the HuF. As determined by ⁵¹Cr release, human mononuclear leukocytes (MNL) were inhibited from mediating ADCC by PGE₁ or E₂ (0.1 µg/ml), PGF₂ or A₁ (1.0 µg/ml), PGB₁ (10 µg/ml), isoproterenol (10^-6 M), theophylline (10^-3 M), methyl-isobutyl-xanthine (10^-4 M), and db-cAMP (10^-4 M). The inhibitory effect these reagents had on ADCC was removed by washing the cells and no adverse effect on viability was noted. Another quantitative ADCC assay, antibody-dependent suppression of plaque formation, also indicated that PGE₂ inhibited MNL-mediated ADCC, and showed the reagent had no effect on virus growth in HuF. Except for the 1.0 µg/ml concentrations of PGF₂ and A₁, the inhibition of ADCC produced by PG was correlated with significant elevations of cAMP in the human MNL. Finally, experiments showed that as the concentration of PGE₂ added to the cultures increased, there was a decrease in both the number of MNL attached to the HuF and the amount of ADCC obtained. Thus, the data indicated that PGE₂ inhibited cytolysis by interfering with attachment of the effector MNL to the antibody-coated target cells. In summary the studies support the proposition PG could cause exacerbation of HSV disease in patients by suppression of ADCC.

Footnotes

¹ This work was supported by Public Health Service Grants 2T0 1GM-00726 and DE04609 from the National Institutes of Health.

² Address correspondence to: Kenneth F. Trofatter, Jr., Box 2865, Duke University Medical Center, Durham, N. C. 27710.