Endotoxin-induced monocytic microparticles have contrasting effects on endothelial inflammatory responses

Area of Science:

• Immunology
• Cell Biology
• Vascular Biology

Background:

• Septic shock involves a life-threatening response to infection, with endothelial cell and monocyte interactions driving microvasculature dysfunction.
• The precise role of monocyte-derived microparticles in septic shock pathogenesis, particularly concerning vascular permeability, remains incompletely understood.

Purpose of the Study:

• To investigate whether microparticles derived from activated monocytes contribute to inflammatory processes and vascular permeability in septic shock.
• To characterize the phenotype and mRNA content of lipopolysaccharide (LPS)-induced monocytic microparticles (mMPs).

Main Methods:

• Human monocytes were stimulated with endotoxin (LPS) to induce microparticle release.
• Phenotypic analysis (CD54 expression) and mRNA content of mMPs were assessed.
• Prothrombin time assays evaluated the procoagulant activity of mMPs.
• Co-incubation of mMPs with human brain endothelial cells (hCMEC/D3) assessed endothelial uptake, microparticle release, signaling pathway modulation (pSrc), and monolayer integrity (impedance and permeability assays).

Main Results:

• LPS stimulation enhanced the release of mMPs with elevated CD54 expression and increased pro-inflammatory cytokine mRNA (TNF, IL-6, IL-8).
• LPS-induced mMPs significantly reduced plasma coagulation time compared to non-stimulated mMPs.
• mMPs were taken up by endothelial cells, enhanced endothelial microparticle release, diminished pSrc signaling, and paradoxically promoted endothelial monolayer tightness.

Conclusions:

• LPS-induced monocytic microparticles exhibit a dual role in septic shock.
• These mMPs possess pro-inflammatory and procoagulant properties.
• Unexpectedly, mMPs also demonstrate a protective function for the endothelium by enhancing monolayer tightness.