Colony stimulating factor 1 receptor (Csf1r) expressing cell ablation in mafia (macrophage-specific Fas-induced apoptosis) mice alters monocyte landscape and atherosclerotic lesion characteristics.

Autor: Medina I; Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands.; Division of Biopharmaceutics, Leiden Academic Center for Drug Research, Leiden, the Netherlands., Wieland EB; Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands., Temmerman L; Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands., Otten JJT; Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands., Bermudez B; Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands., Bot I; Division of Biopharmaceutics, Leiden Academic Center for Drug Research, Leiden, the Netherlands., Rademakers T; MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, the Netherlands., Wijnands E; Central Diagnostic Laboratory, Maastricht University Medical Center, Maastricht, the Netherlands., Schurgers L; Department of Biochemistry, Maastricht University, Maastricht, the Netherlands., Mees B; Department of Vascular Surgery, Maastricht University Medical Center, Maastricht, the Netherlands., van Berkel TJC; Division of Biopharmaceutics, Leiden Academic Center for Drug Research, Leiden, the Netherlands., Goossens P; Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands., Biessen EAL; Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands.; Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, Aachen, Germany.
Jazyk: angličtina
Zdroj: European journal of immunology [Eur J Immunol] 2024 Nov; Vol. 54 (11), pp. e2350943. Date of Electronic Publication: 2024 Sep 04.
DOI: 10.1002/eji.202350943
Abstrakt: Macrophage infiltration and accumulation in the atherosclerotic lesion are associated with plaque progression and instability. Depletion of macrophages from the lesion might provide valuable insights into plaque stabilization processes. Therefore, we assessed the effects of systemic and local macrophage depletion on atherogenesis. To deplete monocytes/macrophages we used atherosclerosis-susceptible Apoe - /- mice, bearing a MaFIA (macrophage-Fas-induced-apoptosis) suicide construct under control of the Csf1r (CD115) promotor, where selective apoptosis of Csf1r-expressing cells was induced in a controlled manner, by administration of a drug, AP20187. Systemic induction of apoptosis resulted in a decrease in lesion macrophages and smooth-muscle cells. Plaque size and necrotic core size remained unaffected. Two weeks after the systemic depletion of macrophages, we observed a replenishment of the myeloid compartment. Myelopoiesis was modulated resulting in an expansion of CSF1R lo myeloid cells in the circulation and a shift from Ly6c hi monocytes toward Ly6c int and Ly6c lo populations in the spleen. Local apoptosis induction led to a decrease in plaque burden and macrophage content with marginal effects on the circulating myeloid cells. Local, but not systemic depletion of Csf1r + myeloid cells resulted in decreased plaque burden. Systemic depletion led to CSF1R lo -monocyte expansion in blood, possibly explaining the lack of effects on plaque development.
(© 2024 The Author(s). European Journal of Immunology published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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