Related Experiment Video
Updated: May 25, 2026
In Vitro Stimulation and Visualization of Extracellular Trap Release in Differentiated Human Monocyte-derived Macrophages
Published on: November 1, 2019
Activation of macrophage-stimulating protein by human airway trypsin-like protease
Hiroshi Orikawa1, Makiko Kawaguchi, Takashi Baba
1Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
Abstract:
Macrophage-stimulating protein (MSP) circulates as a proform protein and requires proteolytic processing for activation. Respiratory ciliated cells express the MSP receptor, recepteur d'origine nantais (RON), at the apical surface, which reportedly has an important role in ciliary function. Like RON, human airway trypsin-like protease (HAT) is also expressed at the apical surface of ciliated cells. Here we show that HAT cleaves proMSP at the physiological activation site, Arg483-Val484. MSP processed by HAT could induce chemotactic responses and morphological changes of peritoneal macrophages. In human respiratory epithelial cells, knock down of HAT expression reduced proMSP processing and RON autophosphorylation. We suggest that HAT is important for MSP-RON signaling in the respiratory tract.
Insights
Human airway trypsin-like protease (HAT) activates macrophage-stimulating protein (MSP) in the respiratory tract. This HAT-mediated activation is crucial for macrophage signaling and ciliary function via the recepteur d
Area of Science:
- Molecular Biology
- Cell Biology
- Respiratory Medicine
Background:
- Macrophage-stimulating protein (MSP) is a proform protein requiring proteolytic cleavage for activation.
- The MSP receptor, recepteur d'origine nantais (RON), is expressed on respiratory ciliated cells and involved in ciliary function.
- Human airway trypsin-like protease (HAT) is also found on the apical surface of respiratory ciliated cells.
Purpose of the Study:
- To investigate the role of HAT in the proteolytic processing and activation of proMSP.
- To determine if HAT-mediated MSP activation influences MSP-RON signaling in respiratory epithelial cells.
Main Methods:
- In vitro cleavage assays to demonstrate HAT's enzymatic activity on proMSP.
- Analysis of MSP processing and RON autophosphorylation in human respiratory epithelial cells with HAT knockdown.
- Assessment of macrophage responses to HAT-processed MSP.
Main Results:
- HAT was shown to cleave proMSP at the physiological activation site (Arg483-Val484).
- HAT-processed MSP induced chemotaxis and morphological changes in peritoneal macrophages.
- Knockdown of HAT in respiratory epithelial cells decreased proMSP processing and RON autophosphorylation.
Conclusions:
- HAT is a key protease responsible for the physiological activation of MSP in the respiratory tract.
- HAT-dependent MSP activation plays a significant role in MSP-RON signaling within the respiratory system.
- These findings highlight HAT's importance in regulating immune cell function and ciliary activity in the airways.
