title: Trans-10, cis-12 conjugated linoleic acid modulates phagocytic responses of canine peripheral blood polymorphonuclear neutrophilic leukocytes exposed to Clostridium difficile toxin B.
abstract: Trans-10, cis-12 conjugated linoleic acid (t10c12-CLA) has been reported to enhance phagocyte function. Clostridium difficile toxin B (TcdB) has been known to inhibit Ras-homologous (Rho) guanosine triphosphatases (GTPases) which play essential roles in neutrophil immune functions. Here, we examined whether in vitro treatment with t10c12-CLA modulates the filamentous actin (F-actin) polymerization, phagocytic capacity, and oxidative burst activity (OBA) of canine peripheral blood polymorphonuclear neutrophilic leukocytes (PMNs) exposed to TcdB. Treatment with t10c12-CLA, but not linoleic acid, enhanced PMN F-actin polymerization, phagocytic capacity, and OBA, while TcdB suppressed these functions. t10c12-CLA reversed the suppressive effects of TcdB on these PMN functions. t10c12-CLA stimulated F-actin polymerization regardless of whether phagocytosis was stimulated by microspheres but only elevated OBA when microspheres were added. We asked whether the effects of t10c12-CLA were associated with changes in the activation of the Rho GTPase Cdc42. Treatment with t10c12-CLA augmented Cdc42 activity in both TcdB-treated and TcdB-naive PMNs during phagocytosis. Thus, t10c12-CLA up-regulates PMN phagocytic responses attenuated by TcdB. This effect is associated with an increase in actin polymerization and may involve the activation of Cdc42.
authors.affiliation: Laboratory of Veterinary Internal Medicine, Department of Veterinary Medicine, College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Ji-Houn
authors.initials: JH
authors.lastname: Kang
authors.forename: Geun-Shik
authors.initials: GS
authors.lastname: Lee
authors.forename: Eui-Bae
authors.initials: EB
authors.lastname: Jeung
authors.forename: Mhan-Pyo
authors.initials: MP
authors.lastname: Yang
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000633:toxicity*; D001427:Bacterial Toxins / Q000633:toxicity*; D001483:Base Sequence; D016360:Clostridioides difficile / Q000276:immunology / Q000472:pathogenicity; D017931:DNA Primers / Q000235:genetics; D004285:Dogs / Q000276:immunology*; D007113:Immunity, Innate / Q000187:drug effects; D066298:In Vitro Techniques; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects*; D016897:Respiratory Burst / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000276:immunology
chemical_list: D000199:Actins; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D017931:DNA Primers; D044243:Linoleic Acids, Conjugated; C031815:toxB protein, Clostridium difficile; C496197:trans-10,cis-12-conjugated linoleic acid; D020764:cdc42 GTP-Binding Protein; D020741:rho GTP-Binding Proteins