Transcellular diapedesis is initiated by invasive podosomes
Christopher V Carman1, Peter T Sage, Tracey E Sciuto
1The CBR Institute for Biomedical Research, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Immunity
|June 16, 2007
Summary
Lymphocytes form transcellular pores through endothelium using invasive podosomes, a process dependent on Src kinase and WASP. This mechanism is crucial for leukocyte trafficking during immune responses.
Area of Science:
- Immunology
- Cell Biology
- Vascular Biology
Background:
- Diapedesis, or leukocyte migration, is vital for immunity and inflammation.
- Leukocytes traverse endothelium via paracellular or transcellular routes.
- Mechanisms of transcellular diapedesis remain poorly understood.
Purpose of the Study:
- To elucidate the mechanisms of transcellular diapedesis.
- To identify the cellular structures and molecular players involved in forming transcellular pores.
Main Methods:
- Utilized advanced microscopy to observe lymphocyte-endothelial interactions.
- Investigated the role of podosomes, Src kinase, WASP, SNARE complex, and intracellular calcium.
Main Results:
- Lymphocytes employ invasive podosomes to create transcellular pores in endothelium.
- Podosome formation requires Src kinase and WASP in lymphocytes.
- Endothelial membrane fusion, involving SNAREs and calcium, facilitates pore formation.
Conclusions:
- Podosomes are key structures for transcellular diapedesis.
- This study reveals novel molecular mechanisms governing leukocyte trafficking.
- Findings offer insights into immune cell migration and podosome function.
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