Neuroprotective effect of Fn14 deficiency is associated with induction of the granulocyte-colony stimulating factor (G-CSF) pathway in experimental stroke and enhanced by a pathogenic human antiphospholipid antibody.
Using a transgenic mouse model of ischemic stroke we checked for a possible interaction of antiphospholipid antibodies (aPL) which often cause thromboses as well as central nervous system (CNS) involvement under non-thrombotic conditions and the TWEAK/Fn14 pathway known to be adversely involved in inflammatory and ischemic brain disease. After 7 days, infarct volumes were reduced in Fn14 deficient mice and were further decreased by aPL treatment. This was associated with strongest increase of the endogenous neuroprotective G-CSF/G-CSF receptor system. This unexpected beneficial action of aPL is an example for a non-thrombogenic action and the double-edged nature of aPL.
Frauenknecht
Katrin
K
Department of Neuropathology, University Medical Center of the Johannes Gutenberg University Mainz, D-55131 Mainz, Germany. katrin.frauenknecht@unimedizin-mainz.de
Bargiotas
Panagiotis
P
Bauer
Henrike
H
von Landenberg
Philipp
P
Schwaninger
Markus
M
Sommer
Clemens
C
D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000009:adverse effects / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis* / Q000502:physiology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011897:Random Allocation; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency* / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics; D000074050:TWEAK Receptor
D017152:Antibodies, Antiphospholipid; D018836:Inflammation Mediators; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D018124:Receptors, Tumor Necrosis Factor; C000613297:TNFRSF12A protein, human; D000074050:TWEAK Receptor; C000613299:Tnfrsf12a protein, mouse; D016179:Granulocyte Colony-Stimulating Factor