Synergistic regulation mechanism of selectin and integrin on leukocyte adhesion under shear flow

2021 ◽  
pp. 1-32
Author(s):  
Wei Kang ◽  
Long Li ◽  
Jizeng Wang
Keyword(s):  
Shear Flow ◽  
Leukocyte Adhesion ◽  
Hydrodynamic Process ◽  
Regulation Mechanism ◽  
Leukocyte Rolling ◽  
Cooperative Effects ◽  
Inflammatory Site ◽  
Synergistic Regulation ◽  
Effective Phase ◽  
Kinetics Of

Abstract In the process of inflammation, the hydrodynamic process of circulating leukocyte recruitment to the inflammatory site requires the rolling adhesion of leukocytes in blood vessels mediated by selectin and integrin molecules. Although a number of experiments have demonstrated that cooperative effects exist between selectins and integrins in leukocyte rolling adhesion under shear flow, the mechanisms underlying how the mechanics of selectins and integrins synergistically may govern the dynamics of cell rolling is not yet fully resolved. Here we present a mechanical model on selectin- and integrin- jointly mediated rolling adhesion of leukocyte in shear flow, by considering two pairs' binding/unbinding events as Markov processes and describing kinetics of leukocyte by the approach of continuum mechanics. Through examining the dynamics of leukocyte rolling as a function of relative fraction of selectin and integrin pairs, we show that, during recruitment, the elongation of intermittent weak selectin bonds consuming the kinetic energy of rolling leukocyte decelerates the rolling speed and enables the integrin pairs to form strong bonds, therefore achieving the arrestment of leukocyte (firm adhesion). The coexistence of selectins and integrins may also be required for effective phase transition from firm adhesion to rolling adhesion, due to dynamic competition in pairs' formation and elongation. These results are verified by the relevant Monte Carlo simulations and related to reported experimental observations.

LAD-III, a leukocyte adhesion deficiency syndrome associated with defective Rap1 activation and impaired stabilization of integrin bonds

Blood ◽  
2004 ◽  
Vol 103 (3) ◽  
pp. 1033-1036 ◽  
Author(s):  
Tatsuo Kinashi ◽  
Memet Aker ◽  
Maya Sokolovsky-Eisenberg ◽  
Valentin Grabovsky ◽  
Chisato Tanaka ◽  
...  
Keyword(s):  
Shear Flow ◽  
Ligand Binding ◽  
Phorbol Esters ◽  
Leukocyte Adhesion ◽  
Deficiency Syndrome ◽  
Small Gtpase ◽  
High Avidity ◽  
Integrin Activation ◽  
Leukocyte Adhesion Deficiency ◽  
Rap1 Activation

AbstractRecently, we reported a rare leukocyte adhesion deficiency (LAD) associated with severe defects in integrin activation by chemokine signals, despite normal ligand binding of leukocyte integrins.1 We now report that the small GTPase, Rap1, a key regulator of inside-out integrin activation is abnormally regulated in LAD Epstein-Barr virus (EBV) lymphocyte cells. Both constitutive and chemokine-triggered activation of Rap1 were abolished in LAD lymphocytes despite normal chemokine signaling. Nevertheless, Rap1 expression and activation by phorbol esters were intact, ruling out an LAD defect in Rap1 guanosine triphosphate (GTP) loading. The very late antigen 4 (VLA-4) integrin abnormally tethered LAD EBV lymphocytes to its ligand vascular cell adhesion molecule 1 (VCAM-1) under shear flow due to impaired generation of high-avidity contacts despite normal ligand binding and intact avidity to surface-bound anti-VLA-4 monoclonal antibody (mAb). Thus, a defect in constitutive Rap1 activation results in an inability of ligand-occupied integrins to generate high-avidity binding to ligand under shear flow. This is a first report of an inherited Rap1 activation defect associated with a pathologic disorder in leukocyte integrin function, we herein term it “LAD-III.” (Blood. 2004;103:1033-1036)

Heat-Sterllized Pd Fluid Blocks Leukocyte Adhesion and Increases Flow Velocity in Rat Peritoneal Venules

1996 ◽  
Vol 16 (1_suppl) ◽  
pp. 137-141 ◽  
Author(s):  
Peter Jonasson ◽  
Ulf Bagge ◽  
Anders Wieslander ◽  
Magnus Braide
Keyword(s):  
Cell Culture ◽  
Blood Flow ◽  
Flow Velocity ◽  
Bacterial Infections ◽  
Degradation Products ◽  
Leukocyte Adhesion ◽  
Microvascular Blood Flow ◽  
Leukocyte Rolling ◽  
Rat Mesentery ◽  
Rolling Leukocytes

Data from cell culture experiments indicate that heat sterilization of peritoneal dialysis (PD) fluids produces cytotoxic glucose degradation products. The present vital microscopic study investigated the effects of different sterilization methods on the biocompatibility of PD fluids. Thus, heat-sterilized (commercially obtained and experimentally produced) and filter-sterilized PD fluids (pH = 5.30 5.40; 1.5% glucose) were compared with Tyrode buffer, with respect to the effects on microvascular blood flow velocity and leukocyte adhesion in the rat mesentery. Exteriorization of the mesentery produced a mild inflammation, known from the literature and characterized by the adhesive rolling of leukocytes along venular walls. Superfusion of the mesentery with filter-sterilized PD fluid had no significant effects on leukocyte rolling or flow velocity in venules 25 40 μm in diameter compared with buffer superfusion. Heat-sterilized PD fluid decreased the concentration of rolling leukocytes and increased flow velocity significantly, as compared with buffer and filter-sterilized PD fluid. The results indicate that heat sterilization of PD fluids produces substances that interact with microvascular tone and leukocyte-endothelial adhesion, which hypothetically could impair the acute, granulocyte-mediated defense against bacterial infections.

Endothelial E- and P-selectin expression in iNOS- deficient mice exposed to polymicrobial sepsis

2001 ◽  
Vol 280 (2) ◽  
pp. G291-G297 ◽  
Author(s):  
Cameron W. Lush ◽  
Gediminas Cepinskas ◽  
William J. Sibbald ◽  
Peter R. Kvietys
Keyword(s):  
Leukocyte Adhesion ◽  
Cecal Ligation ◽  
Leukocyte Rolling ◽  
Wild Type ◽  
Endothelial Adhesion Molecule ◽  
Acute Peritonitis ◽  
Leukocyte Accumulation ◽  
Deficient Mice

In vitro, nitric oxide (NO) decreases leukocyte adhesion to endothelium by attenuating endothelial adhesion molecule expression. In vivo, lipopolysaccharide-induced leukocyte rolling and adhesion was greater in inducible NO synthase (iNOS)−/− mice than in wild-type mice. The objective of this study was to assess E- and P-selectin expression in the microvasculature of iNOS−/− and wild-type mice subjected to acute peritonitis by cecal ligation and perforation (CLP). E- and P-selectin expression were increased in various organs within the peritoneum of wild-type animals after CLP. This CLP-induced upregulation of E- and P-selectin was substantially reduced in iNOS−/− mice. Tissue myeloperoxidase (MPO) activity was increased to a greater extent in the gut of wild-type than in iNOS−/− mice subjected to CLP. In the lung, the reduced expression of E-selectin in iNOS−/− mice was not associated with a decrease in MPO. Our findings indicate that NO derived from iNOS plays an important role in sepsis-induced increase in selectin expression in the systemic and pulmonary circulation. However, in iNOS−/− mice, sepsis-induced leukocyte accumulation is affected in the gut but not in the lungs.

Leukocyte adhesion in local versus hemorrhage-induced ischemia

1992 ◽  
Vol 263 (3) ◽  
pp. H810-H815 ◽  
Author(s):  
M. A. Perry ◽  
D. N. Granger
Keyword(s):  
Endothelial Cell ◽  
Leukocyte Adhesion ◽  
Ischemia Reperfusion ◽  
Leukocyte Rolling ◽  
Leukocyte Adherence ◽  
Rolling Velocity ◽  
Local Ischemia ◽  
Cell Adhesive ◽  
Local Restriction ◽  
Adhesive Interactions

The objective of this study was to compare the leukocyte-endothelial cell adhesive interactions elicited in postcapillary venules by either local ischemia-reperfusion or hemorrhage-reperfusion. Leukocyte rolling, adherence, and emigration were monitored in cat mesenteric venules exposed to an 85% reduction in blood flow (induced by either hemorrhage or local restriction of arterial inflow) for 1 h, followed by 1 h reperfusion. Leukocyte-endothelial cell interactions, venular diameter, and red blood cell velocity were measured during baseline, ischemia, and reperfusion periods. Both local and hemorrhage-induced ischemia reperfusion caused a reduction in leukocyte rolling velocity and increases in leukocyte adherence and emigration. Quantitatively, the adherence and emigration responses in both ischemia models were nearly identical. However, the two models differed in their response to immunoneutralization of the leukocyte adhesion glycoprotein CD11/CD18 with monoclonal antibody (MAb) IB4. The MAb had a more profound effect in attenuating leukocyte adherence and emigration in the local ischemia model. These results indicate that different factors may contribute to leukocyte-endothelial cell adhesive interactions observed in local vs. systemic models of ischemia-reperfusion.

Hydrodynamics and Leukocyte Adhesion in Microvessels: State of the Art

2008 ◽  
Author(s):  
Josa Hanzlik ◽  
Ellen Cretekos ◽  
Kathleen A. Lemkin-Kennard
Keyword(s):  
Leukocyte Adhesion ◽  
Ultrasound Contrast Agents ◽  
Great Promise ◽  
Computational Techniques ◽  
Leukocyte Rolling ◽  
Complex Flow ◽  
Nano Fabrication ◽  
Physiological Processes ◽  
Targeted Ultrasound ◽  
Novel Devices

Leukocyte rolling and adhesion are complex physiological processes that have received a great deal of attention over the past decade. Significant increases in the knowledge base related to how leukocytes adhere in shear flows have occurred as a result of the development of novel experimental and computational techniques. Micro- and nano-fabrication techniques have enabled the development of novel flow devices for studying leukocyte adhesion in simple and complex geometries. Improvements in computer technology have enabled simulations of complex flow processes to be developed. As a result of these advances in knowledge related to leukocyte adhesion, numerous novel devices have been developed that mimic the leukocyte rolling and adhesion process. Examples of these devices include cell separation and enrichment devices and targeted ultrasound contrast agents. Future advances related to leukocyte rolling and adhesion processes hold great promise for advancing our knowledge of disease processes as well as development of novel therapeutic devices.

scholarly journals Fucoidin, but not yeast polyphosphomannan PPME, inhibits leukocyte rolling in venules of the rat mesentery

Blood ◽  
1993 ◽  
Vol 81 (1) ◽  
pp. 177-185 ◽  
Author(s):  
K Ley ◽  
G Linnemann ◽  
M Meinen ◽  
LM Stoolman ◽  
P Gaehtgens
Keyword(s):  
Leukocyte Adhesion ◽  
Sulfated Polysaccharides ◽  
Leukocyte Rolling ◽  
Lymphocyte Homing ◽  
High Endothelial Venules ◽  
Lymphocyte Adhesion ◽  
Adhesion Receptor ◽  
Rat Mesentery ◽  
Rolling Leukocytes ◽  
Rolling Leukocyte

Abstract Leukocyte rolling in venules is inhibited by several sulfated polysaccharides, by antibodies to the leukocyte adhesion receptor L- selectin (LECAM-1), and by recombinant soluble L-selectin. The sulfated fucose polymer fucoidin and the polyphosphomannan PPME bind to L- selectin and inhibit L-selectin-mediated lymphocyte adhesion to lymph node high endothelial venules (LN-HEV). We investigated whether fucoidin and PPME also inhibit leukocyte rolling. Rolling leukocyte flux was determined by intravital microscopy in 47 venules (diameter 21 to 50 microns) of the rat mesentery with and without micro-infusion of each reagent through 8-microns glass micropipettes. Micro-infusion (1 mg/mL) or intravenous (IV) injection (25 mg/kg) of fucoidin, but not vehicle, reduced leukocyte rolling by greater than 90%. The half- effective concentration was approximately 2.5 micrograms/mL. Stroboscopic fluorescence video microscopy showed that fucoidin decreased the fraction of rolling leukocytes from 44% of all leukocytes passing the venules in control to less than 1%. PPME micro-infusion (1 mg/mL) or IV injection (14 mg/kg) did not reduce leukocyte rolling. Hence, leukocyte rolling differs from lymphocyte homing with respect to the effect of PPME. This may be related to fucoidin binding to L- selectin with greater affinity than PPME. Alternatively, inflamed venular endothelium may express a ligand for L-selectin different from that constitutively expressed on LN-HEV.

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