التفاصيل البيبلوغرافية
| العنوان: |
Intravascular adhesion and recruitment of neutrophils in response to CXCL1 depends on their TRPC6 channels. |
| المؤلفون: |
Lindemann, Otto, Rossaint, Jan, Najder, Karolina, Schimmelpfennig, Sandra, Hofschröer, Verena, Wälte, Mike, Fels, Benedikt, Oberleithner, Hans, Zarbock, Alexander, Schwab, Albrecht |
| المصدر: |
Journal of Molecular Medicine; Mar2020, Vol. 98 Issue 3, p349-360, 12p |
| مصطلحات موضوعية: |
NEUTROPHILS, BONE marrow cells, INTEGRINS, ATOMIC force microscopy, ADHESION, REPERFUSION injury, GRANULOCYTES |
| مستخلص: |
Here we report a novel role for TRPC6, a member of the transient receptor potential (TRPC) channel family, in the CXCL1-dependent recruitment of murine neutrophil granulocytes. Representing a central element of the innate immune system, neutrophils are recruited from the blood stream to a site of inflammation. The recruitment process follows a well-defined sequence of events including adhesion to the blood vessel walls, migration, and chemotaxis to reach the inflammatory focus. A common feature of the underlying signaling pathways is the utilization of Ca2+ ions as intracellular second messengers. However, the required Ca2+ influx channels are not yet fully characterized. We used WT and TRPC6−/− neutrophils for in vitro and TRPC6−/− chimeric mice (WT mice with WT or TRPC6−/− bone marrow cells) for in vivo studies. After renal ischemia and reperfusion injury, TRPC6−/− chimeric mice had an attenuated TRPC6−/− neutrophil recruitment and a better outcome as judged from the reduced increase in the plasma creatinine concentration. In the cremaster model CXCL1-induced neutrophil adhesion, arrest and transmigration were also decreased in chimeric mice with TRPC6−/− neutrophils. Using atomic force microscopy and microfluidics, we could attribute the recruitment defect of TRPC6−/− neutrophils to the impact of the channel on adhesion to endothelial cells. Mechanistically, TRPC6−/− neutrophils exhibited lower Ca2+ transients during the initial adhesion leading to diminished Rap1 and β2 integrin activation and thereby reduced ICAM-1 binding. In summary, our study reveals that TRPC6 channels in neutrophils are crucial signaling modules in their recruitment from the blood stream in response to CXCL1. Key point: Neutrophil TRPC6 channels are crucial for CXCL1-triggered activation of integrins during the initial steps of neutrophil recruitment. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
