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Endothelial LSP1 is involved in endothelial dome formation, minimizing vascular permeability changes during neutrophil transmigration in vivo
- Source :
- Blood. 117(3)
- Publication Year :
- 2010
-
Abstract
- The endothelium actively participates in neutrophil migration out of the vasculature via dynamic, cytoskeleton-dependent rearrangements leading to the formation of transmigratory cups in vitro, and to domes that completely surround the leukocyte in vivo. Leukocyte-specific protein 1 (LSP1), an F-actin–binding protein recently shown to be in the endothelium, is critical for effective transmigration, although the mechanism has remained elusive. Herein we show that endothelial LSP1 is expressed in the nucleus and cytosol of resting endothelial cells and associates with the cytoskeleton upon endothelial activation. Two-photon microscopy revealed that endothelial LSP1 was crucial for the formation of endothelial domes in vivo in response to neutrophil chemokine keratinocyte-derived chemokine (KC) as well as in response to endogenously produced chemokines stimulated by cytokines (tumor necrosis factor α [TNFα] or interleukin-1β [IL-1β]). Endothelial domes were significantly reduced in Lsp1−/− compared with wild-type (WT) mice. Lsp1−/− animals not only showed impaired neutrophil emigration after KC and TNFα stimulation, but also had disproportionate increases in vascular permeability. We demonstrate that endothelial LSP1 is recruited to the cytoskeleton in inflammation and plays an important role in forming endothelial domes thereby regulating neutrophil transendothelial migration. The permeability data may underscore the physiologic relevance of domes and the role for LSP1 in endothelial barrier integrity.
- Subjects :
- Male
Pathology
medicine.medical_specialty
Mice, 129 Strain
Endothelium
Neutrophils
Immunology
Blotting, Western
Green Fluorescent Proteins
Vascular permeability
Biology
Granulocyte
Biochemistry
Endothelial activation
Capillary Permeability
Mice
Microscopy, Electron, Transmission
medicine
Animals
Humans
Muscle, Skeletal
Cells, Cultured
Cytoskeleton
Mice, Knockout
Microscopy, Confocal
Tumor Necrosis Factor-alpha
Calcium-Binding Proteins
Microfilament Proteins
Transendothelial and Transepithelial Migration
Endothelial Cells
Cell Biology
Hematology
Cell biology
Endothelial stem cell
Vascular endothelial growth factor B
Mice, Inbred C57BL
Vascular endothelial growth factor A
medicine.anatomical_structure
Microscopy, Fluorescence, Multiphoton
Vascular endothelial growth factor C
Female
Subjects
Details
- ISSN :
- 15280020
- Volume :
- 117
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....ec295c6c1bf70b480ab0e044e3678929