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Pyrrolomycin group antibiotics inhibit substance P-induced release of myeloperoxidase from human polymorphonuclear leukocytes.

1991; Springer Nature; Volume: 44; Issue: 5 Linguagem: Inglês

10.7164/antibiotics.44.533

1881-1469

Kaori Masuda, Kazuo Suzuki, Akiko Ishida‐Okawara, Satoshi Mizuno, Kunimoto Hotta, Shinji Miyadoh, Osamu Hara, M. Koyama,

Neutrophil, Myeloperoxidase and Oxidative Mechanisms

In order to search for microbial modulators of the activity of neuropeptide, we established a screen based on substance P (SP)-induced myeloperoxidase (MPO) release from human polymorphonuclear leukocytes (PMN). SP induced MPO release in a dose-dependent manner at concentrations ranging from 1-10 × 10-4M. In comparison at 1 × 10-4M, induction was also observed with SP derivatives but not with other neuropeptides such as neurokinin and enkephalin. Based on this, we searched for microbial inhibitors against SP-induced MPO release. An actinomycete metabolite designated HS3, which turned out to be identical with dioxapyrrolomycin or A1-R2081, and structurally related pyrrolomycins were found to inhibit SP-induced MPO release. In addition, these compounds inhibited the f-Met-Leu-Phe (FMLP)-induced MPO release from PMlfl. Pyrrolomycin derivatives with an N-methylated pyrrole ring showed, however, a selective inhibition of the SP-induced MPO release. This was in contrast to results with aseanostatin P5 which selectively inhibited FMLP-induced MPO release.