期刊
JOURNAL OF IMMUNOLOGY
卷 201, 期 9, 页码 2602-2611出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1800249
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资金
- Medical Research Council U.K. [MR/K013386/1]
- Chief Scientist Office [ETM330]
- Engineering and Physical Sciences Research Council
- Medical Research Council Centre for Doctoral Training in Optical Medical Imaging, OPTIMA [EP/L016559/1]
- MRC [MR/K013386/1, G0601481] Funding Source: UKRI
Resolution of the inflammatory response requires coordinated regulation of pro- and anti-inflammatory mediator production, together with clearance of recruited inflammatory cells. Many different receptors have been implicated in phagocytosis of apoptotic cells (efferocytosis), including Mer, a receptor tyrosine kinase that can mediate recognition and subsequent internalization of apoptotic cells. In this manuscript, we examine the expression and function of the Tyro3/Axl/Mer (TAM) family of receptors by human monocytes. We demonstrate that the Mer ligand, protein S, binds to the surface of viable monocytes via phosphatidylserine-dependent and -independent mechanisms. Importantly, we have identified a novel role for receptor tyrosine kinase signaling in the augmentation of monocyte cytokine release in response to LPS. We propose that low-level phosphatidylserine exposure on the plasma membrane of viable monocytes allows protein S binding that leads to TAM-dependent augmentation of proinflammatory cytokine production. Our findings identify a potentially important role for TAM-mediated signaling during the initiation phase of inflammation.
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