Please use this identifier to cite or link to this item: doi:10.22028/D291-38322
Title: Macrophage Polarization is Deregulated in Haemophilia
Author(s): Knowles, Lynn M.
Kagiri, Daniela
Bernard, Martin
Schwarz, Eva C.
Eichler, Hermann
Pilch, Jan
Language: English
Title: Thrombosis and Haemostasis
Volume: 119
Issue: 2
Pages: 234-245
Publisher/Platform: Thieme
Year of Publication: 2019
Free key words: haemophilia
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: Macrophages make important contributions to inflammation and wound healing. We show here that macrophage polarization is deregulated in haemophilia in response to macrophage colony-stimulating factor (M-CSF) and partially in response to granulocyte-macrophage colony-stimulating factor (GM-CSF). As a result, haemophilia macrophages exhibit a specific impairment of M-CSF-mediated functions involved in wound healing such as clot invasion and phagocytosis. Haemophilia monocytes express reduced amounts of the receptors for M-CSF and GM-CSF, which correlates with a failure to express tumour necrosis factor α (TNFα) and CD163 in M-CSF-treated haemophilia macrophages and reduced expression of TNFα and CD206 after treatment with GM-CSF. Protein expression in response to M-CSF was regained with respect to CD163 and CD206 after embedding haemophilia monocytes in clotted plasma suggesting that a functioning coagulation system has positive effects on macrophage M2 polarization. Mimicking the functional deficits of haemophilia macrophages in normal macrophages was possible by adding leptin, which we found to be elevated in the blood of haemophilia patients, to a monocyte cell line. The increase of leptin occurred in conjunction with C-reactive protein in a body mass index-controlled cohort suggesting that haemophilia patients harbour chronic low-grade inflammation. Together, our data indicate that impaired clotting in haemophilia patients leads to increased inflammation and a deregulation in macrophage differentiation, which may explain the commonly observed deficits in wound healing and tissue regeneration.
DOI of the first publication: 10.1055/s-0038-1676796
URL of the first publication:
Link to this record: urn:nbn:de:bsz:291--ds-383223
ISSN: 2567-689X
Date of registration: 1-Dec-2022
Description of the related object: Supplementary Material
Related object:
Faculty: M - Medizinische Fakultät
Department: M - Biophysik
M - Chirurgie
Professorship: M - Prof. Dr. Hermann Eichler
M - Keiner Professur zugeordnet
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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