The bone marrow endothelial progenitor cell response to septic infection

Document Type

Article

Publication Date

4-3-2024

Publication Title

Frontiers in Immunology

Abstract

Early increase in the level of endothelial progenitor cells (EPCs) in the systemic circulation occurs in patients with septic infection/sepsis. The significance and underlying mechanisms of this response remain unclear. This study investigated the bone marrow EPC response in adult mice with septic infection induced by intravenous injection (i.v.) of . For experiments, sorted marrow stem/progenitor cells (SPCs) including lineage(lin)stem cell factor receptor (c-kit)stem cell antigen-1 (Sca-1), linc-kit, and lin cells were cultured with or without lipopolysaccharides (LPSs) and recombinant murine vascular endothelial growth factor (VEGF) in the absence and presence of anti-Sca-1 crosslinking antibodies. In a separate set of experiments, marrow linc-kit cells from green fluorescence protein (GFP) mice, i.v. challenged with heat-inactivated or saline for 24 h, were subcutaneously implanted in Matrigel plugs for 5 weeks. Marrow linc-kit cells from Sca-1 knockout (KO) mice challenged with heat-inactivated for 24 h were cultured in the Matrigel medium for 8 weeks. The marrow pool of EPCs bearing the linc-kitSca-1VEGF receptor 2 (VEGFR2) (LKS VEGFR2) and LKS CD133VEGFR2 surface markers expanded rapidly following septic infection, which was supported by both proliferative activation and phenotypic conversion of marrow stem/progenitor cells. Increase in marrow EPCs and their reprogramming for enhancing angiogenic activity correlated with cell-marked upregulation of Sca-1 expression. Sca-1 was coupled with Ras-related C3 botulinum toxin substrate 2 (Rac2) in signaling the marrow EPC response. Septic infection caused a substantial increase in plasma levels of IFN-γ, VEGF, G-CSF, and SDF-1. The early increase in circulating EPCs was accompanied by their active homing and incorporation into pulmonary microvasculature. These results demonstrate that the marrow EPC response is a critical component of the host defense system. Sca-1 signaling plays a pivotal role in the regulation of EPC response in mice with septic infection.

PubMed ID

38665923

Volume

15

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