title: Discovery of mitocryptide-1, a neutrophil-activating cryptide from healthy porcine heart.
abstract: Although neutrophils are known to migrate in response to various chemokines and complement factors, the substances involved in the early stages of their transmigration and activation have been poorly characterized to date. Here we report the discovery of a peptide isolated from healthy porcine hearts that activated neutrophils. Its primary structure is H-Leu-Ser-Phe-Leu-Ile-Pro-Ala-Gly-Trp-Val-Leu-Ser-His-Leu-Asp-His-Tyr-Lys-Arg-Ser-Ser-Ala-Ala-OH, and it was indicated to originate from mitochondrial cytochrome c oxidase subunit VIII. This peptide caused chemotaxis at concentrations lower than that inducing beta-hexosaminidase release. Such responses were observed in neutrophilic/granulocytic differentiated HL-60 cells but not in undifferentiated cells, and G(i2)-type G proteins were suggested to be involved in the peptide signaling. Moreover the peptide activated human neutrophils to induce beta-hexosaminidase secretion. A number of other amphipathic neutrophil-activating peptides presumably originating from mitochondrial proteins were also found. The present results suggest that neutrophils monitor such amphipathic peptides including the identified peptide as an initiation signal for inflammation at injury sites.
authors.affiliation: Institute of Applied Biochemistry, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan. hmukai-endo@umin.ac.jp
authors.forename: Hidehito
authors.initials: H
authors.lastname: Mukai
authors.forename: Yoshinori
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authors.lastname: Hokari
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Seki
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Takao
authors.forename: Makoto
authors.initials: M
authors.lastname: Kubota
authors.forename: Yuko
authors.initials: Y
authors.lastname: Matsuo
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsukagoshi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kato
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kimura
authors.forename: Yasutsugu
authors.initials: Y
authors.lastname: Shimonishi
authors.forename: Yoshiaki
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authors.lastname: Kiso
authors.forename: Yoshisuke
authors.initials: Y
authors.lastname: Nishi
authors.forename: Kaori
authors.initials: K
authors.lastname: Wakamatsu
authors.forename: Eisuke
authors.initials: E
authors.lastname: Munekata