Arsiwala, Tasneem; Vogt, Anne-Cathrine S.; Barton, Amy E; Manolova, Vania; Funk, Felix; Flühmann, Beat; Bachmann, Martin F. (2022). Kupffer Cells and Blood Monocytes Orchestrate the Clearance of Iron-Carbohydrate Nanoparticles from Serum. International journal of molecular sciences, 23(5) MDPI 10.3390/ijms23052666
|
Text
ijms-23-02666-v2.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (14MB) | Preview |
Intravenous (IV) iron nanoparticle preparations are widely used to treat iron deficiency. The mechanism of mononuclear phagocyte system-mediated clearance of IV iron nanoparticles is unknown. The early uptake and homeostasis of iron after injection of ferric carboxymaltose (FCM) in mice was studied. An increase in serum iron was observed at 2.5 h followed by a return to baseline by 24 h. An increase in circulating monocytes was observed, particularly Ly6Chi and Ly6Clow. FCM was also associated with a time-dependent decrease in liver Kupffer cells (KCs) and increase in liver monocytes. The increase in liver monocytes suggests an influx of iron-rich blood monocytes, while some KCs underwent apoptosis. Adoptive transfer experiments demonstrated that following liver infiltration, blood monocytes differentiated to KCs. KCs were also critical for IV iron uptake and biodegradation. Indeed, anti-Colony Stimulating Factor 1 Receptor (CSF1R)-mediated depletion of KCs resulted in elevated serum iron levels and impaired iron uptake by the liver. Gene expression profiling indicated that C-C chemokine receptor type 5 (CCR5) might be involved in monocyte recruitment to the liver, confirmed by pharmaceutical inhibition of CCR5. Liver KCs play a pivotal role in the clearance and storage of IV iron and KCs appear to be supported by the expanded blood monocyte population.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie 04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology and Immunology |
UniBE Contributor: |
Arsiwala, Tasneem Gulam Abbas, Vogt, Anne-Cathrine Sarah, Bachmann, Martin (B) |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1422-0067 |
Publisher: |
MDPI |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
11 Mar 2022 11:29 |
Last Modified: |
29 Mar 2023 23:38 |
Publisher DOI: |
10.3390/ijms23052666 |
PubMed ID: |
35269805 |
Uncontrolled Keywords: |
Kupffer cells biodisposition ferric carboxymaltose iron nanomedine monocytes |
BORIS DOI: |
10.48350/167207 |
URI: |
https://boris.unibe.ch/id/eprint/167207 |
Actions (login required)
 |
Edit item |