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Inhibition of neutrophil superoxide production by fanetizole

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Abstract

The effects on neutrophil function of the new immunomodulatory agent fanetizole mesylate were studied. Fanetizole did not affect random or stimulated migration, phagocytosis, or degranulation by normal human neutrophils. Production of superoxide in response to the chemotactic factor formyl-methionyl-leucyl-phenylalanine (f-Met-Leu-Phe) was markedly inhibited (41.3±3.9%) by 250μM fanetizole. This inhibition was not due to scavenging of superoxide by fanetizole, as there was no impairment of superoxide detection in a cell-free xanthine-xanthine oxidase system. Inhibition was dose dependent (no effect seen with 1 or 10μM fanetizole) and stimulus specific (no impairment of superoxide production in response to phorbol myristate acetate). Washing the cells after fanetizole treatment partially restored their superoxide response to f-Met-Leu-Phe. Suppression of neutrophil production of toxic oxygen metabolites may partially explain the antiarthritic effect of fanetizole, and study of such selective inhibitors may be useful in probing the contribution of neutrophils to inflammatory tissue damage.

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Authors and Affiliations

  1. Divisions of Experimental Medicine, Tufts University School of Medicine, 02111, Boston, Massachusetts

    Barbara Styrt & Mark S. Klempner

  2. Divisions of Experimental Allergy, Tufts University School of Medicine, 02111, Boston, Massachusetts

    Ross E. Rocklin

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  1. Barbara Styrt
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  2. Ross E. Rocklin
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  3. Mark S. Klempner
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Additional information

Part of this work has been published in abstract form (Clinical Research 32:469A, 1984). Supported in part by grant AI16732 from the National Institutes of Health and a Charlton Fund grant from Tufts University School of Medicine.

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Styrt, B., Rocklin, R.E. & Klempner, M.S. Inhibition of neutrophil superoxide production by fanetizole. Inflammation 9, 233–244 (1985). https://doi.org/10.1007/BF00916274

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