title: Neutrophil F-actin dynamics in Familial Mediterranean Fever: the unequal effect of colchicine on activated neutrophils.
abstract: In the innate immune system, cellular adaptation regulates neutrophil activation and chemotaxis, which have a pivotal role in Familial Mediterranean Fever (FMF) pathogenesis. We investigated neutrophil F-actin, phagocytosis and macropinocytosis dynamics during neutrophil chemoattractant-dependent activation in FMF patients carrying mutations in the MEFV locus. We found that while a non-stimulated neutrophil shows an increased overall F-actin content in patients with FMF, the activation-dependent F-actin dynamics in the presence of chemoattractant peptide is significantly reduced. Neither overall F-actin content nor F-actin dynamics was changed in FMF patient's neutrophils in the presence of double doses of chemoattractant, while in healthy donors it occurred with significant reduction of F-actin content and dynamics. The neutrophil shows increased phagocytosis and macropinocytosis dynamics for a relatively short period, which may contribute to the decreasing of plasticity of the cellular cytoskeleton during FMF. Colchicine causes reduction of overall F-actin content and shows a distinctively unequal effect on chemoattractant-activated neutrophil F-actin dynamics in FMF patients compared with healthy donors. These data suggested that mutations in MEFV cause the dissolution of cellular adaptation to chemoattractant stimuli due to alterations in neutrophil F-actin and phagocytosis dynamics, which could serve as a major target for FMF treatment.
authors: Laboratory of Immunology and Virology, "Armenicum" Research Centre, CJSC Armenicum, 37 Nalbandyan str., Yerevan 0001, Republic of Armenia. tigdav@excite.com
authors: Tigran K
authors: TK
authors: Davtyan
authors: Samvel A
authors: SA
authors: Avetisyan
authors: Gagik S
authors: GS
authors: Hakobyan
mesh_terms: D000199:Actins / Q000235:genetics / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D002633:Chemotaxis / Q000235:genetics / Q000276:immunology; D003078:Colchicine / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D010505:Familial Mediterranean Fever / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D018375:Neutrophil Activation / Q000235:genetics / Q000276:immunology*; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology; D000071198:Pyrin; D055815:Young Adult
chemical_list: D000199:Actins; D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D000071198:Pyrin; D003078:Colchicine