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2017 ; 2
(10
): ä Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Experimental lupus is aggravated in mouse strains with impaired induction of
neutrophil extracellular traps
#MMPMID28515366
Kienhöfer D
; Hahn J
; Stoof J
; Csepregi JZ
; Reinwald C
; Urbonaviciute V
; Johnsson C
; Maueröder C
; Podolska MJ
; Biermann MH
; Leppkes M
; Harrer T
; Hultqvist M
; Olofsson P
; Munoz LE
; Mocsai A
; Herrmann M
; Schett G
; Holmdahl R
; Hoffmann MH
JCI Insight
2017[May]; 2
(10
): ä PMID28515366
show ga
Many effector mechanisms of neutrophils have been implicated in the pathogenesis
of systemic lupus erythematosus (SLE). Neutrophil extracellular traps (NETs) have
been assigned a particularly detrimental role. Here we investigated the
functional impact of neutrophils and NETs on a mouse model of lupus triggered by
intraperitoneal injection of the cell death-inducing alkane pristane.
Pristane-induced lupus (PIL) was aggravated in 2 mouse strains with impaired
induction of NET formation, i.e., NOX2-deficient (Ncf1-mutated) and peptidyl
arginine deiminase 4-deficient (PAD4-deficient) mice, as seen from elevated
levels of antinuclear autoantibodies (ANAs) and exacerbated glomerulonephritis.
We observed a dramatically reduced ability to form pristane-induced NETs in vivo
in both Ncf1-mutated and PAD4-deficient mice, accompanied by higher levels of
inflammatory mediators in the peritoneum. Similarly, neutropenic Mcl-1?Myelo mice
exhibited higher levels of ANAs, which indicates a regulatory function in lupus
of NETs and neutrophils. Blood neutrophils from Ncf1-mutated and human
individuals with SLE exhibited exuberant spontaneous NET formation. Treatment
with specific chemical NOX2 activators induced NET formation and ameliorated PIL.
Our findings suggest that aberrant NET is one of the factors promoting
experimental lupus-like autoimmunity by uncontrolled release of inflammatory
mediators.