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Flow Cytometry-based Assay for the Monitoring of NK Cell Functions
Published on: October 30, 2016
Signaling pathways regulating CD44-dependent cytolysis in natural killer cells
G Sconocchia1, J A Titus, D M Segal
1The Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1360, USA.
Blood
|July 15, 1997
Summary
Natural killer (NK) cells use CD44 to trigger cell killing (CD44DL) after activation. This process requires new protein synthesis, perforin release, PI 3-kinase, and actin polymerization for effective lysis.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- CD44 is a molecule found on activated natural killer (NK) cells.
- Its role in triggering cytotoxicity (CD44-directed lysis or CD44DL) in NK cells is not fully understood.
- Understanding the molecular mechanisms of CD44DL is crucial for NK cell-based immunotherapies.
Purpose of the Study:
- To investigate the metabolic pathways and molecular requirements for CD44-directed lysis (CD44DL) in activated human NK cells.
- To elucidate the signaling pathways, including kinase and cytoskeleton involvement, that regulate CD44DL.
Main Methods:
- Used activated human NK cells as effectors to study CD44DL.
- Employed inhibitors such as Concanimycin A, kinase inhibitors, wortmannin, and cytochalasin B to dissect the cytolytic pathways.
- Analyzed the role of de novo protein expression and actin polymerization in CD44DL.
Main Results:
- CD44DL requires de novo protein expression and perforin release, similar to natural cytotoxicity and antibody-dependent cell-mediated cytolysis (ADCC).
- Protein-tyrosine and ser/thr kinases are essential for CD44DL, natural cytotoxicity, and ADCC, while protein kinase C is nonessential.
- Phosphatidylinositol 3-kinase (PI 3-kinase) is specifically required for CD44DL, and actin polymerization modulates this process.
Conclusions:
- CD44 interacts with newly expressed proteins in activated NK cells to initiate a triggering pathway for CD44DL.
- This pathway involves perforin release, requires PI 3-kinase activity, and is modulated by the actin cytoskeleton.
- The findings provide insights into the regulation of NK cell cytotoxicity mediated by CD44.
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