scholarly journals Two-dimensional kinetics of β2-integrin and ICAM-1 bindings between neutrophils and melanoma cells in a shear flow

2008 ◽  
Vol 294 (3) ◽  
pp. C743-C753 ◽  
Author(s):  
Shile Liang ◽  
Changliang Fu ◽  
Desiree Wagner ◽  
Huiguang Guo ◽  
Dongying Zhan ◽  
...  
Keyword(s):  
Shear Flow ◽  
Melanoma Cells ◽  
Polymorphonuclear Neutrophils ◽  
Wall Region ◽  
Lymphocyte Function ◽  
Specific Receptor ◽  
Color Flow ◽  
Receptor Ligand ◽  
Ligand Interactions ◽  
Kinetics Of

Cell adhesion, mediated by specific receptor-ligand interactions, plays an important role in biological processes such as tumor metastasis and inflammatory cascade. For example, interactions between β2-integrin (lymphocyte function-associated antigen-1 and/or Mac-1) on polymorphonuclear neutrophils (PMNs) and ICAM-1 on melanoma cells initiate the bindings of melanoma cells to PMNs within the tumor microenvironment in blood flow, which in turn activate PMN-melanoma cell aggregation in a near-wall region of the vascular endothelium, therefore enhancing subsequent extravasation of melanoma cells in the microcirculations. Kinetics of integrin-ligand bindings in a shear flow is the determinant of such a process, which has not been well understood. In the present study, interactions of PMNs with WM9 melanoma cells were investigated to quantify the kinetics of β2-integrin and ICAM-1 bindings using a cone-plate viscometer that generates a linear shear flow combined with a two-color flow cytometry technique. Aggregation fractions exhibited a transition phase where it first increased before 60 s and then decreased with shear durations. Melanoma-PMN aggregation was also found to be inversely correlated with the shear rate. A previously developed probabilistic model was modified to predict the time dependence of aggregation fractions at different shear rates and medium viscosities. Kinetic parameters of β2-integrin and ICAM-1 bindings were obtained by individual or global fittings, which were comparable to respectively published values. These findings provide new quantitative understanding of the biophysical basis of leukocyte-tumor cell interactions mediated by specific receptor-ligand interactions under shear flow conditions.

scholarly journals Interaction of leukocyte integrins with ligand is necessary but not sufficient for function.

1992 ◽  
Vol 116 (6) ◽  
pp. 1527-1535 ◽  
Author(s):  
I Dransfield ◽  
C Cabañas ◽  
J Barrett ◽  
N Hogg
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Killer Cell ◽  
Inhibitory Effect ◽  
T Cell Proliferation ◽  
Lymphocyte Function ◽  
Receptor Ligand ◽  
Leukocyte Integrins ◽  
Cell Assays ◽  
Ligand Interactions

The leukocyte integrins (CD11/CD18 or beta 2-type integrins) are expressed exclusively on leukocytes and participate in many adhesion-dependent functions (Arnaout, M.A. 1990. Blood. 75:1037-1050; Springer, T. A. 1990. Nature. (Lond.) 346:425-434; Dustin, M. L., and T. S. Springer. 1991. Annu. Rev. Immunol. 9:27-66). The avidity of leukocyte integrin binding to their ligands or counter-receptors is dependent upon response to intracellular signals (Wright, S. D., and B. C. Meyer. 1986. J. Immunol. 136:1759-1764; Dustin, M. A., and T. S. Springer. 1989. Nature (Lond.). 341:619-624). We have investigated the effects of a novel mAb (mAb 24) which defines a leukocyte integrin alpha subunit epitope that is Mg(2+)-dependent and may be used as a "reporter" of the activation state of these receptors (Dransfield, I., and N. Hogg. 1989. EMBO (Eur. Mol. Biol. Organ) J. 8:3759-3765; Dransfield, I., A.-M. Buckle, and N. Hogg. 1990. Immunol. Rev. 114:29-44; Dransfield, I., C. Cabañas, A. Craig, and N. Hogg. 1992. J. Cell Biol.) Data is presented to show that this mAb inhibits monocyte-dependent, antigen-specific T cell proliferation and IL-2-activated natural killer cell assays which are both dependent on lymphocyte function-associated antigen-1 (LFA-1), and complement receptor type 3 (CR3)-mediated neutrophil chemotaxis to f-Met-Leu-Phe. This inhibitory effect is not caused by the prevention of receptor/ligand binding because LFA-1/ICAM-1, LFA-1/ICAM-2,3 and CR3/iC3b interactions are, under activating conditions, promoted rather than blocked by mAb 24. As it does not interfere with mitogen-stimulated T cell proliferation, it is unlikely that mAb 24 transduces a "negative" or antiproliferative signal to the T cells to which it is bound. Using a model system of transient activation of LFA-1, we have found that mAb 24 prevents "deadhesion" of receptor/ligand pairs, possibly locking leukocyte integrins in an "active" conformation. It is speculated that inhibition of leukocyte integrin function by this mAb reflects the necessity for dynamic leukocyte integrin/ligand interactions.

Covalently Immobilizing Interferon-γ Drives Filopodia Production through Specific Receptor–Ligand Interactions Independently of Canonical Downstream Signaling

2020 ◽  
Vol 31 (5) ◽  
pp. 1362-1369 ◽  
Author(s):  
Shaun M. Christie ◽  
Trevor R. Ham ◽  
Grant T. Gilmore ◽  
Paul D. Toth ◽  
Nic D. Leipzig ◽  
...  
Keyword(s):  
Interferon Γ ◽  
Specific Receptor ◽  
Receptor Ligand ◽  
Downstream Signaling ◽  
Ligand Interactions

scholarly journals NK Cell Recognition and Killing of Melanoma Cells Is Controlled by Multiple Activating Receptor-Ligand Interactions

2011 ◽  
Vol 3 (4) ◽  
pp. 365-373 ◽  
Author(s):  
Sara Morgado ◽  
Beatriz Sanchez-Correa ◽  
Javier G. Casado ◽  
Esther Duran ◽  
Inmaculada Gayoso ◽  
...  
Keyword(s):  
Nk Cell ◽  
Melanoma Cells ◽  
Cell Recognition ◽  
Receptor Ligand ◽  
Ligand Interactions ◽  
Activating Receptor ◽  
Nk Cell Recognition

scholarly journals Combined modeling of cell aggregation and adhesion mediated by receptor–ligand interactions under shear flow

2015 ◽  
Vol 5 (6) ◽  
pp. 216-221 ◽  
Author(s):  
Yu Du ◽  
Shuang Peng ◽  
Yuhong Cui ◽  
Shouqin Lü ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Shear Flow ◽  
Cell Aggregation ◽  
Receptor Ligand ◽  
Ligand Interactions

scholarly journals Distinct role of hydrodynamic shear in leukocyte-facilitated tumor cell extravasation

2005 ◽  
Vol 288 (4) ◽  
pp. C831-C839 ◽  
Author(s):  
Margaret J. Slattery ◽  
Shile Liang ◽  
Cheng Dong
Keyword(s):  
Shear Stress ◽  
Shear Rate ◽  
Melanoma Cell ◽  
Melanoma Cells ◽  
Polymorphonuclear Neutrophils ◽  
Lymphocyte Function ◽  
Migration Assay ◽  
Hydrodynamic Shear ◽  
Multistep Process ◽  
Functional Blocking

Previously, we found polymorphonuclear neutrophils (PMNs) increased melanoma cell extravasation under flow conditions ( Intl J Cancer 106: 713–722, 2003). In this study, we characterized the effect of hydrodynamic shear on PMN-facilitated melanoma extravasation using a novel flow-migration assay. The effect of shear stress and shear rate on PMN-facilitated melanoma extravasation was studied by increasing the medium viscosity with dextran to increase shear stress independently of shear rate. Under fixed shear rate conditions, melanoma cell extravasation did not change significantly. In contrast, the extravasation level increased at a fixed shear stress but with a decreasing shear rate. PMN-melanoma aggregation and adhesion to the endothelium via β2-integrin/intracellular adhesion molecule-1 (ICAM-1) interactions were also studied. Lymphocyte function-associated molecule-1 (LFA-1; CD11a/CD18) influenced the capture phase of PMN binding to both melanoma cells and the endothelium, whereas Mac-1 (CD11b/CD18) affected prolonged PMN-melanoma aggregation. Blockage of E-selectin or ICAM-1 on the endothelium or ICAM-1 on the melanoma surface reduced PMN-facilitated melanoma extravasation. We have found PMN-melanoma adhesion is correlated with the inverse of shear rate, whereas the PMN-endothelial adhesion correlated with shear stress. Interleukin-8 (IL-8) also influenced PMN-melanoma cell adhesion. Functional blocking of the PMN IL-8 receptors, CXCR1 and CXCR2, decreased the level of Mac-1 upregulation on PMNs while in contact with melanoma cells and reduced melanoma extravasation. We have found PMN-facilitated melanoma adhesion to be a complex multistep process that is regulated by both microfluid mechanics and biology.

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