Heightened endotoxin susceptibility of monocytes and neutrophils during familial Mediterranean fever.
Familial Mediterranean fever (FMF) is a relapsing autoinflammatory disorder, caused by various mutations in the MEFV gene, which encodes a protein called pyrin, expressed in neutrophils and activated monocytes. Induction of monocyte endotoxin tolerance is observed in FMF patients during attack, whereas monocytes from patients in the attack-free period failed to induce lipopolysaccharide tolerance and exhibited heightened sensitivity to bacterial endotoxin. In this study, we demonstrated that impaired lipopolysaccharide tolerance induction in attack-free FMF patients correlates with both increased lipopolysaccharide-induced proinflammatory cytokine synthesis polarization and a different time-course pattern of lipopolysaccharide-induced changes on monocytic surface expression of CD14 and CD11b coreceptors. We found that this pattern is characterized either by delayed turnover of CD14 or increased surface retention of CD11b receptors on monocytes during stimulation with lipopolysaccharide. In addition, enhancement of lipopolysaccharide-induced apoptosis of neutrophils was observed in FMF patients, and was confirmed based on the fact that neutrophils from FMF patients previously unexposed to Salmonella enteritidis exhibited heightened susceptibility to the lipopolysaccharide of this pathogen similar to that of patients infected with this species.
Davtyan
Tigran K
TK
Armenicum Research Centre, CJSC Armenicum, Yerevan, Republic of Armenia. tigdav@excite.com
Harutyunyan
Vachagan A
VA
Hakobyan
Gagik S
GS
Avetisyan
Samvel A
SA
D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D004731:Endotoxins / Q000494:pharmacology*; D010505:Familial Mediterranean Fever / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D009000:Monocytes / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism
D004731:Endotoxins