scholarly journals Macropinocytosis overcomes directional bias due to hydraulic resistance to enhance space exploration by dendritic cells

2018 ◽  
Author(s):  
Hélène D. Moreau ◽  
Carles Blanch-Mercader ◽  
Rafaele Attia ◽  
Zahraa Alraies ◽  
Mathieu Maurin ◽  
...  

SummaryThe migration of immune cells is guided by specific chemical signals, such as chemokine gradients. Their trajectories can also be diverted by physical cues and obstacles imposed by the cellular environment, such as topography, rigidity, adhesion, or hydraulic resistance. On the example of hydraulic resistance, it was shown that neutrophil preferentially follow paths of least resistance, a phenomenon referred to as barotaxis. We here combined quantitative imaging and physical modeling to show that barotaxis results from a force imbalance at the scale of the cell, which is amplified by the acto-myosin intrinsic polarization capacity. Strikingly, we found that macropinocytosis specifically confers to immature dendritic cells a unique capacity to overcome this physical bias by facilitating external fluid transport across the cell, thereby enhancing their space exploration capacity in vivo and promoting their tissue-patrolling function. Conversely, mature dendritic cells, which down-regulate macropinocytosis, were found to be sensitive to hydraulic resistance. Theoretical modeling suggested that barotaxis, which helps them avoid dead-ends, may accelerate their migration to lymph nodes, where they initiate adaptive immune responses. We conclude that the physical properties of the microenvironment of moving cells can introduce biases in their migratory behaviors but that specific active mechanisms such as macropinocytosis have emerged to diminish the influence of these biases, allowing motile cells to reach their final destination and efficiently fulfill their functions.

Author(s):  
HHllne D. Moreau ◽  
Carles Blanch-Mercader ◽  
Rafaele Attia ◽  
Zahraa Alraies ◽  
Mathieu Maurin ◽  
...  

2019 ◽  
Vol 49 (2) ◽  
pp. 171-188.e5 ◽  
Author(s):  
Hélène D. Moreau ◽  
Carles Blanch-Mercader ◽  
Rafaele Attia ◽  
Mathieu Maurin ◽  
Zahraa Alraies ◽  
...  

Author(s):  
Thomas Krucker ◽  
Britto S. Sandanaraj

Optical technologies used in biomedical research have undergone tremendous development in the last decade and enabled important insight into biochemical, cellular and physiological phenomena at the microscopic and macroscopic level. Historically in drug discovery, to increase throughput in screening, or increase efficiency through automation of image acquisition and analysis in pathology, efforts in imaging were focused on the reengineering of established microscopy solutions. However, with the emergence of the new grammar for drug discovery, other requirements and expectations have created unique opportunities for optical imaging. The new grammar of drug discovery provides rules for translating the wealth of genomic and proteomic information into targeted medicines with a focus on complex interactions of proteins. This paradigm shift requires highly specific and quantitative imaging at the molecular level with tools that can be used in cellular assays, animals and finally translated into patients. The development of fluorescent targeted and activatable ‘smart’ probes, fluorescent proteins and new reporter gene systems as functional and dynamic markers of molecular events in vitro and in vivo is therefore playing a pivotal role. An enabling optical imaging platform will combine optical hardware refinement with a strong emphasis on creating and validating highly specific chemical and biological tools.


2001 ◽  
Vol 86 (11) ◽  
pp. 1257-1263 ◽  
Author(s):  
Attilio Bondanza ◽  
Angelo Manfredi ◽  
Valérie Zimmermann ◽  
Matteo Iannacone ◽  
Angela Tincani ◽  
...  

SummaryScavenger phagocytes are mostly responsible for the in vivo clearance of activated or senescent platelets. In contrast to other particulate substrates, the phagocytosis of platelets does not incite pro-inflammatory responses in vivo. This study assessed the contribution of macrophages and dendritic cells (DCs) to the clearance of activated platelets. Furthermore, we verified whether antibodies against the β2 Glycoprotein I (β2GPI), which bind to activated platelets, influence the phenomenon. DCs did not per se internalise activated platelets. In contrast, macrophages efficiently phagocytosed platelets. In agreement with the uneventful nature of the clearance of platelets in vivo, phagocytosing macrophages did not release IL-1β, TNF-α or IL-10. β2GPI bound to activated platelets and was required for their recognition by anti-ββ2GPI antibodies. DCs internalised platelets opsonised by anti-ββ2GPI antibodies. The phagocytosis of opsonised platelets determined the release of TNF-α and IL-1β by DCs and macrophages. Phagocytosing macrophages, but not DCs, secreted the antiinflammatory cytokine IL-1β0. We conclude that anti-ββ2GPI antibodies cause inflammation during platelet clearance and shuttle platelet antigens to antigen presenting DCs.


Sign in / Sign up

Export Citation Format

Share Document