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Extravasating Neutrophil-derived Microparticles Preserve Vascular Barrier Function in Inflamed Tissue.

ABSTRACT: Emerging evidence suggests that gap formation and opening of the endothelial junctions during leukocyte extravasation is actively controlled to maintain the integrity of the vascular barrier. While the role for endothelial cells to this process has been well defined, it is not clear whether leukocytes are also actively contributing to endothelial barrier function. We have recently showed that extravasating leukocytes deposit microparticles on the subendothelium during the late stages of extravasation, which is LFA-1 dependent. Using multiphotonintravital microscopy (MP-IVM) of mouse cremaster muscle vessels in the current work, we show that microparticle formation and deposition maintains the integrity of the microvascular barrier during leukocyte extravasation. Inhibition of neutrophil-derived microparticle formation resulted in dramatically increased vascular leakage. These findings suggest that deposition of microparticles during neutrophil extravasation is essential for maintaining endothelial barrier function and may result in temporal difference between neutrophil extravasation and an increase in vascular leakage.

SUBMITTER: Lim K

PROVIDER: S-EPMC3718920 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Biological materials derived from the extracellular matrix (ECM) of tissues serve as scaffolds for rebuilding tissues and for improved wound healing. Cornea trauma represents a wound healing challenge as the default repair pathway can result in fibrosis and scar formation that limit vision. Effective treatments are needed to reduce inflammation, promote tissue repair, and retain the tissue's native transparency and vision capacity. Tissue microparticles derived from cornea, cartilage and lymph nodes were processed and screened in vitro for their ability to reduce inflammation in ocular surface cells isolated from the cornea stroma, conjunctiva, and lacrimal gland. Addition of ECM particles to the media reduced expression of inflammatory genes and restored certain tear film protein production in vitro. Particles derived from lymph nodes were then applied to a rabbit lamellar keratectomy corneal injury model. Application of the tissue particles in a fibrin glue carrier decreased expression of inflammatory and fibrotic genes and scar formation as measured through imaging, histology and immunohistochemistry. In sum, immunomodulatory tissue microparticles may provide a new therapeutic tool for reducing inflammation in the cornea and ocular surface and promoting tissue repair. STATEMENT OF SIGNIFICANCE: Damaged cornea will result in scar tissue formation that impedes vision, and new therapies are needed to enhance wound healing in the cornea and to prevent fibrosis. We evaluated the effects of biological scaffolds derived extracellular matrix (ECM) during corneal wound healing. These ECM particles reduced inflammatory gene expression and restored tear film production in vitro, and reduced scar formation and fibrosis genes in the wounded cornea, when applied to in vivo lamellar keratectomy injury model. The immunomodulatory tissue microparticles may provide a new therapeutic tool for reducing inflammation in the cornea and ocular surface and promoting proper tissue repair.

Dataset Information

Extravasating Neutrophil-derived Microparticles Preserve Vascular Barrier Function in Inflamed Tissue.

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