Characterization of a monoclonal antibody that neutralizes the activity of prostaglandin E2

S. J. Mnich, A. W. Veenhuizen, J. B. Monahan, K. C.F. Sheehan, K. R. Lynch, P. C. Isakson, J. P. Portanova

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Abstract

We describe the generation of an IgG1 mAb, 2B5, that neutralizes the biologic activity of PGE2 in vitro and in vivo. The Ab was derived from a BALB/c mouse that was immunized with a PGE2-thyroglobulin conjugate. 2B5 is one of the highest affinity and specific anti-PGE2 mAbs reported to date. The K(d) for PGE2 was approximately 300 pM and crossreactivity toward eicosanoids other than PGE1 was less than 1%. The addition of 2B5 to [3H]PGE2 blocked the binding of radioligand to cell membranes transfected with the murine EP3 prostaglandin receptor. In functional studies, 2B5 neutralized the capacity of PGE2 to suppress T cell proliferation induced by a mitogenic anti-CD3 Ab in vitro. In contrast, immunosuppression by the phosphodiesterase inhibitor, isobutylmethylxanthine was not affected. In an in vive model of nociception, 2B5 substantially reduced the dorsoflexion response of mice to phenylbenzoquinone. This response is associated with prostaglandin production and is blocked by inhibitors of prostanoid synthesis. Our findings demonstrate that this nociceptive response is largely due to PGE2. In the absence of antagonists that prevent PGE2 from activating a diverse family of receptor subtypes, neutralizing Abs to PGE2 should represent useful reagents to delineate the biologic properties of this eicosanoid in vivo.

Original languageEnglish
Pages (from-to)4437-4444
Number of pages8
JournalJournal of Immunology
Volume155
Issue number9
StatePublished - Jan 1 1995
Externally publishedYes

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    Mnich, S. J., Veenhuizen, A. W., Monahan, J. B., Sheehan, K. C. F., Lynch, K. R., Isakson, P. C., & Portanova, J. P. (1995). Characterization of a monoclonal antibody that neutralizes the activity of prostaglandin E2. Journal of Immunology, 155(9), 4437-4444.