Intravascular Leukocyte Chemotaxis: The Rules of Attraction

Massena, Sara; Phillipson, Mia

doi:10.5772/35840

Cited by 3 publications

(6 citation statements)

References 135 publications

(175 reference statements)

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“…Leukocytes eventually cross the endothelium -an event called diapedesis -and reach targeted zones via connective tissues. At vessels inner walls, leukocytes crawl distances of several tens or hundreds of micrometers, proposedly in search for optimal diapedesis sites (1)(2)(3). Diapedesis seems indeed to occur at specialized area of the endothelium, called "Cuplike" transmigratory structures (4) or "portals" (3).…”

Section: Introductionmentioning

confidence: 99%

“…Directed motion is a hallmark of the immune response. Leukocytes are sensitive to mechanical cues like blood flow (mechanotaxis) (5)(6)(7)(8), to soluble biochemical cues like bacterial fragments or chemokines (chemotaxis) (1,9), and to anchored signaling molecules like chemokines CCL21 or IL8 (haptotaxis) (10)(11)(12). However, if directed motion by adhesion molecules (adhesive haptotaxis) is well documented for cancer cells, fibroblasts, endothelial cells or neurons (13)(14)(15)(16)(17)(18)(19)(20)(21)(22), it has not been evidenced for leukocytes yet.…”

Section: Introductionmentioning

confidence: 99%

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Different integrins mediate haptotaxis of T lymphocytes towards either lower or higher adhesion zones

Aoun

Biarnes-Pelicot

et al. 2019

Preprint

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Guidance of cells by molecules anchored on a substrate, known as haptotaxis, is arguably crucial in development, immunology and cancer, however the exact cues and mechanisms driving cell orientation in vivo are hardly identified. Adhesive haptotaxis has been described in the case of mesenchymatous cells that develop strong pulling forces with their substrates and orient via a tug of war mechanism -a competition between cells' pulling edges. In the case of amoeboid cells that migrate with minimal interaction with their substrate, existence of adhesive haptotaxis remains unclear. Here, we studied the crawling of human T lymphocytes on substrates with spatially modulated adhesivity, and observed haptotaxis with surface concentrations of integrin ligands found on high endothelial veinules. Overexpression of ICAM-1 and VCAM-1 molecules observed in vivo at transmigration portals can therefore promote leukocyte recruitment. Mechanistically, we show that integrin-mediated haptotaxis of lymphocytes differ both from active chemotaxis, because no mechanotransduction was detected, and from the passive tug of war mechanism of mesenchymatous cells, because different integrins support opposite phenotypes. Cells favored more adherent zones with VLA-4 and, counterintuitively, less adherent zones with LFA-1. These results reveal that integrins control differential adhesive haptotaxis behaviors without mechanotransduction, and this smart capability may support unsuspected ways for cells path selection.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Different integrins mediate haptotaxis of T lymphocytes towards either lower or higher adhesion zones

Aoun

Biarnes-Pelicot

et al. 2019

Preprint

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“…Leukocytes arrest on the endothelium of blood vessels -the cellular monolayer covering the lumen -, then migrate spontaneously with a rapid 'crawling' mode, and eventually cross the endothelium -an event called diapedesis. On blood vessels walls, leukocytes crawl distances of several tens or hundreds of micrometers, proposedly in search for optimal diapedesis sites (Massena and Phillipson, 2012; called "transmigratory cups" (Carman and Springer, 2004) or "portals" . These sites are composed of endothelial cells with vertical microvilli-like projections enriched in adhesion molecules, notably the integrin ligands ICAM-1 (intercellular adhesion molecule-1) and VCAM-1 (vascular cell adhesion molecule-1).…”

Section: Introductionmentioning

confidence: 99%

“…Directed motion is a hallmark of the immune response and several guiding cues are well identified. Leukocytes are sensitive to mechanical cues like the blood flow (mechanotaxis) (Dominguez et al, 2015;Gorina et al, 2014;Valignat et al, 2013;Valignat et al, 2014), to soluble biochemical cues like bacterial fragments or chemokines (chemotaxis) (Liu et al, 2012;Malawista et al, 2000;Malet-Engra et al, 2015;Massena and Phillipson, 2012;Poznansky et al, 2000;Tharp et al, 2006), and to anchored signaling molecules like the chemokines CCL21 or IL8 (haptotaxis) (Canton, 2008;Roy et al, 2017;Schwarz et al, 2017;van Gils et al, 2013;Weber et al, 2013). Directed motion by adhesion molecules is documented for mesenchymal cells like cancer cells, fibroblasts, muscle cells, endothelial cells (King et al, 2016;MacNearney et al, 2016;Oudin et al, 2016;Wen et al, 2015;Wu et al, 2012) as well as for Schwann cells (Motta et al, 2019) and neurons (Aznavoorian et al, 1990;Brandley and Schnaar, 1989;Carter, 1965;Carter, 1967;Klominek et al, 1993;Mccarthy and Furcht, 1984;O'Connor et al, 1990;Smith et al, 2004;Thibault et al, 2007), but it has not been evidenced yet for amoeboid cells in general and for leukocytes in particular.…”

Section: Introductionmentioning

confidence: 99%

Lymphocytes perform reverse adhesive haptotaxis mediated by LFA-1 integrins

Luo

Noray

Aoun

et al. 2020

Journal of Cell Science

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Cell guidance by anchored molecules, or haptotaxis, is crucial in development, immunology and cancer. Adhesive haptotaxis, or guidance by adhesion molecules, is well established for mesenchymal cells such as fibroblasts, whereas its existence remains unreported for amoeboid cells that require less or no adhesion in order to migrate. We show that, in vitro, amoeboid human T lymphocytes develop adhesive haptotaxis mediated by densities of integrin ligands expressed by high endothelial venules. Moreover, lymphocytes orient towards increasing adhesion with VLA-4 integrins (also known as integrin α4β1), like all mesenchymal cells, but towards decreasing adhesion with LFA-1 integrins (also known as integrin αLβ4), which has not previously been observed. This counterintuitive ‘reverse haptotaxis’ cannot be explained by existing mechanisms of mesenchymal haptotaxis involving either competitive anchoring of cell edges under tension or differential integrin-activated growth of lamellipodia, because they both favor orientation towards increasing adhesion. The mechanisms and functions of amoeboid adhesive haptotaxis remain unclear; however, multidirectional integrin-mediated haptotaxis might operate around transmigration ports on endothelia, stromal cells in lymph nodes, and inflamed tissue where integrin ligands are spatially modulated.

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“…The method used by the MAD simulation to calculate rigid body motion, the Completed Double Layer-Boundary Integral Equation Method (CDL-BIEM), is one that can be applied to any arbitrarily shaped particle as long as its surface is continuous and relatively smooth, and it is well suited to model circulating tumor microemboli [28,29]. The use of a model system with linear shear flow and a flat plane serves as a representation of the flow conditions in linear portions of blood vessels, where the estimated range of blood flow forces are shear rates between 150–1600 s −1 , and resultant shear stresses between 0.8 and 4 dyne/cm 2 , depending on the vessel size and blood flow rate [30,31]. Prior numerical models successfully replicated the formation and maintenance of CTC aggregates in flow [32–36], but they are lacking in information on the interaction of aggregates with the endothelium.…”

Section: Introductionmentioning

confidence: 99%

Effect of circulating tumor cell aggregate configuration on hemodynamic transport and wall contact

Anderson

Guillebon

Hughes

et al. 2017

Mathematical Biosciences

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Selectin-mediated adhesion of circulating tumor cells (CTCs) to the endothelium is a critical step in cancer metastasis, a major factor contributing to the mortality of cancer. The formation of tethers between tumor cells and endothelial selectins initiates cell rolling, which can lead to firm adhesion, extravasation and the formation of secondary metastases. Tumor cells travel through the bloodstream as single cells, or as aggregates known as circulating tumor microemboli (CTM). CTM have increased survivability and metastatic potential relative to CTCs, and the presence of CTM is associated with worse patient prognosis. The motion of cells and cellular aggregates in flow is a function of their size and shape, and these differences influence the frequency and strength of their contact with the endothelium. In this study, a computational model consisting of the hydrodynamic component of the Multiparticle Adhesive Dynamics simulation analyzed the effects of model aggregate conformation and orientation on adhesive binding potential. Model aggregates of the Colo205 colorectal cancer cell line were created, consisting of two, three, and four cells in simple geometrical conformations. Contact time, contact area, and time integral of contact area were measured as a function of fluid shear rate, initial centroid height, and initial orientation for model aggregates that experienced hydrodynamic collisions with the plane wall. It was found that larger CTM conformations with intermediate nonsphericities had the highest adhesion potential. The results of this study shed light on the correlation between environmental conditions and extravasation efficiency, which could inform the development of new anti-metastatic drugs.

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Intravascular Leukocyte Chemotaxis: The Rules of Attraction

Cited by 3 publications

References 135 publications

Different integrins mediate haptotaxis of T lymphocytes towards either lower or higher adhesion zones

Different integrins mediate haptotaxis of T lymphocytes towards either lower or higher adhesion zones

Lymphocytes perform reverse adhesive haptotaxis mediated by LFA-1 integrins

Effect of circulating tumor cell aggregate configuration on hemodynamic transport and wall contact

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