Biopolym. Cell. 2011; 27(5):354-358.
http://dx.doi.org/10.7124/bc.000122
Mutations in MEFV cause alterations in neutrophil F-actin and phagocytosis dynamics
1Davtyan T. K., 2Avetisyan S. A., 2Hakobyan G. S.
  1. "Armenicum" Research Centre, CJSC Armenicum
    37, Nalbandyan Str., Yerevan, Republic of Armenia, 0001
  2. Yerevan State Medical University named after Mkhitar Heratsi, Ministry of Education and Science of Republic of Armenia
    2, Koryun Str., Yerevan, Republic of Armenia, 0025

Abstract

Aim. To examine neutrophil F-actin, phagocytosis and macropinocytosis dymanics in patients with Familial Mediterranean Fever (FMF), in an effort to understand the mechanisms that regulate switch of neutrophil activation program. Methods. Whole blood neutrophils obtained from 37 attack-free FMF patients and 20 normal donors (ND) were activated with N-formyl-Met-Leu-Phe (fMLP), phorbolmyristate acetate (PMA) or lipo- polysaccharide (LPS) and cellular F-actin content, phagocytosis and macropinocytosis determined by flow cytometry. F-actin oscillation amplitude and period were calculated from the curves generated by mathematical simulation giving the assumption that in neutrophil F-actin oscillates about a fixed point in a harmonic motion. Results. Unstimulated neutrophil F-actin content was markedly increased in FMF patients. fMLP- but not PMA- or LPS-stimulated and Col-pretreated neutrophils where characterized by different pattern of F-actin dynamics and delayed time period of F-actin oscillation during FMF. Neutrophils from FMF patients failed to induce chemoattractant receptor desensitization during repeated action of fMLP, while in ND it occurred with significant reduction of F-actin oscillation amplitude and period. In FMF patients we observed significant enhancement of phagocytosis but not macropinocytosis amplitude and frequency. Conclusions. Impaired neutrophil F-actin, phagocytosis and macropinocytosis oscillations amplitude and frequency that tightly regulate switch of neutrophil activation program during its encounter with increasing concentration of chemoattractants may be a potential pathogenic mechanism causing aberrant resolution of inflammation during FMF.
Keywords: familial Mediterranean fever, neutrophil, F-actin, phagocytosis, macropinocytosis, N-formyl-Met-Leu-Phe, phorbolmyristate acetate
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