Enhanced Pro-apoptotic Effects of Fe(II)-Modified IVIG on Human Neutrophils.

Graeter, Stefanie; Schneider, Christoph; Verschoor, Daniëlle; von Däniken, Sandro; Seibold, Frank; Yawalkar, Nikhil; Villiger, Peter; Dimitrov, Jordan D; Smith, David F; Cummings, Richard D; Simon, Hans-Uwe; Vassilev, Tchavdar; von Gunten, Stephan (2020). Enhanced Pro-apoptotic Effects of Fe(II)-Modified IVIG on Human Neutrophils. Frontiers in immunology, 11(973), p. 973. Frontiers Research Foundation 10.3389/fimmu.2020.00973

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Mild modification of intravenous immunoglobulin (IVIG) has been reported to result in enhanced polyspecificity and leveraged therapeutic effects in animal models of inflammation. Here, we observed that IVIG modification by ferrous ions, heme or low pH exposure, shifted the repertoires of specificities in different directions. Ferrous ions exposed Fe(II)-IVIG, but not heme or low pH exposed IVIG, showed increased pro-apoptotic effects on neutrophil granulocytes that relied on a FAS-dependent mechanism. These effects were also observed in human neutrophils primed by inflammatory mediators or rheumatoid arthritis joint fluid in vitro, or patient neutrophils ex vivo from acute Crohn's disease. These observations indicate that IVIG-mediated effects on cells can be enhanced by IVIG modification, yet specific modification conditions may be required to target specific molecular pathways and eventually to enhance the therapeutic potential.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Graeter, Stefanie Rebecca; Verschoor, Daniëlle; von Däniken, Sandro Urs; Yawalkar, Nikhil; Villiger, Peter; Simon, Hans-Uwe and von Gunten, Stephan

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1664-3224

Publisher:

Frontiers Research Foundation

Language:

English

Submitter:

Celine Joray

Date Deposited:

29 Jun 2020 15:32

Last Modified:

05 Jul 2020 02:43

Publisher DOI:

10.3389/fimmu.2020.00973

PubMed ID:

32508840

Uncontrolled Keywords:

FAS cell death inflammation modified IVIG neutrophil

BORIS DOI:

10.7892/boris.144912

URI:

https://boris.unibe.ch/id/eprint/144912

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