leukocyte rolling


Summary: Movement of tethered, spherical LEUKOCYTES along the endothelial surface of the microvasculature. The tethering and rolling involves interaction with SELECTINS and other adhesion molecules in both the ENDOTHELIUM and leukocyte. The rolling leukocyte then becomes activated by CHEMOKINES, flattens out, and firmly adheres to the endothelial surface in preparation for transmigration through the interendothelial cell junction. (From Abbas, Cellular and Molecular Immunology, 3rd ed)

Top Publications

  1. Ley K, Laudanna C, Cybulsky M, Nourshargh S. Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol. 2007;7:678-89 pubmed
    ..This Review focuses on new aspects of one of the central paradigms of inflammation and immunity--the leukocyte adhesion cascade. ..
  2. Rossaint J, Spelten O, Kässens N, Mueller H, Van Aken H, Singbartl K, et al. Acute loss of renal function attenuates slow leukocyte rolling and transmigration by interfering with intracellular signaling. Kidney Int. 2011;80:493-503 pubmed publisher
    ..Acute loss of renal function resulted in cessation of selectin-induced slow leukocyte rolling on E-selectin/intercellular adhesion molecule 1 (ICAM-1) and P-selectin/ICAM-1...
  3. Tang J, Ley K, Hunt C. Dynamics of in silico leukocyte rolling, activation, and adhesion. BMC Syst Biol. 2007;1:14 pubmed
    ..and then operated in ways that represent the molecular and cellular mechanisms believed responsible for leukocyte rolling and adhesion. The result is an in silico analogue of an experimental in vitro system...
  4. Hidalgo A, Peired A, Wild M, Vestweber D, Frenette P. Complete identification of E-selectin ligands on neutrophils reveals distinct functions of PSGL-1, ESL-1, and CD44. Immunity. 2007;26:477-489 pubmed publisher
    ..These results suggest distinct and dynamic contributions of these three glycoproteins in selectin-mediated neutrophil adhesion and signaling. ..
  5. Phillipson M, Heit B, Colarusso P, Liu L, Ballantyne C, Kubes P. Intraluminal crawling of neutrophils to emigration sites: a molecularly distinct process from adhesion in the recruitment cascade. J Exp Med. 2006;203:2569-75 pubmed
    ..e., LFA-1-dependent adhesion followed by Mac-1-dependent crawling, and both steps ultimately contribute to efficient emigration out of the vasculature. ..
  6. Sperandio M, Pickard J, Unnikrishnan S, Acton S, Ley K. Analysis of leukocyte rolling in vivo and in vitro. Methods Enzymol. 2006;416:346-71 pubmed
    b>Leukocyte rolling is an important step for the successful recruitment of leukocytes from blood to tissues mediated by a specialized group of glycoproteins termed selectins...
  7. Smith D, Deem T, Bruce A, Reutershan J, Wu D, Ley K. Leukocyte phosphoinositide-3 kinase {gamma} is required for chemokine-induced, sustained adhesion under flow in vivo. J Leukoc Biol. 2006;80:1491-9 pubmed
    ..We conclude that the gamma isoform of PI-3K must be functional in leukocytes to allow efficient adhesion from rolling in response to chemokine stimulation. ..
  8. Herman C, Potts G, Michael M, Tolan N, Bailey R. Probing dynamic cell-substrate interactions using photochemically generated surface-immobilized gradients: application to selectin-mediated leukocyte rolling. Integr Biol (Camb). 2011;3:779-91 pubmed publisher
    ..to generate surface-immobilized biomolecular gradients that are applied to the study of selectin-mediated leukocyte rolling. The technique employs benzophenone-modified glass substrates, which upon controlled exposure to UV light (..
  9. Zarbock A, Ley K, McEver R, Hidalgo A. Leukocyte ligands for endothelial selectins: specialized glycoconjugates that mediate rolling and signaling under flow. Blood. 2011;118:6743-51 pubmed publisher
    ..Although the physiologic characterization of these ligands has been obtained in mice, we also note reported similarities and differences with human selectin ligands. ..

More Information


  1. Chesnutt B, Smith D, Raffler N, Smith M, White E, Ley K. Induction of LFA-1-dependent neutrophil rolling on ICAM-1 by engagement of E-selectin. Microcirculation. 2006;13:99-109 pubmed
    ..The data show that neutrophil rolling on E-selectin leads to partial activation of LFA-1, enabling LFA-1-dependent rolling on ICAM-1. This mechanism is likely to amplify and accelerate neutrophil recruitment in inflammation. ..
  2. Wojciechowski J, Sarelius I. Preferential binding of leukocytes to the endothelial junction region in venules in situ. Microcirculation. 2005;12:349-59 pubmed
    ..The authors speculate that this reflects movement to those EC junctional regions that support transendothelial migration. ..
  3. Carvalho R, Pellizzon C, Justulin L, Felisbino S, Vilegas W, Bruni F, et al. Effect of mangiferin on the development of periodontal disease: involvement of lipoxin A4, anti-chemotaxic action in leukocyte rolling. Chem Biol Interact. 2009;179:344-50 pubmed publisher
    ..Our results have demonstrated promising therapeutic potential of mangiferin both in the prevention and treatment of periodontitis. ..
  4. Sundd P, Pospieszalska M, Cheung L, Konstantopoulos K, Ley K. Biomechanics of leukocyte rolling. Biorheology. 2011;48:1-35 pubmed publisher
    b>Leukocyte rolling on endothelial cells and other P-selectin substrates is mediated by P-selectin binding to P-selectin glycoprotein ligand-1 expressed on the tips of leukocyte microvilli...
  5. Russell F, Schuelert N, Veldhoen V, Hollenberg M, McDougall J. Activation of PAR(2) receptors sensitizes primary afferents and causes leukocyte rolling and adherence in the rat knee joint. Br J Pharmacol. 2012;167:1665-78 pubmed publisher
    ..The PAR(2) receptors are involved in chronic arthritis by mechanisms that are as yet unclear. Here, we examined PAR(2) activation in the rat knee joint...
  6. Hyduk S, Cybulsky M. Role of alpha4beta1 integrins in chemokine-induced monocyte arrest under conditions of shear stress. Microcirculation. 2009;16:17-30 pubmed publisher
  7. Alon R, Ley K. Cells on the run: shear-regulated integrin activation in leukocyte rolling and arrest on endothelial cells. Curr Opin Cell Biol. 2008;20:525-32 pubmed publisher
    ..Different leukocyte subsets appear to use different modalities of integrin activation during rolling and arrest at distinct endothelial sites. ..
  8. Zarbock A, Ley K. Mechanisms and consequences of neutrophil interaction with the endothelium. Am J Pathol. 2008;172:1-7 pubmed
    ..This Review is focused on the signaling events during the interaction of neutrophils with the endothelium. ..
  9. Zarbock A, Ley K. Neutrophil adhesion and activation under flow. Microcirculation. 2009;16:31-42 pubmed publisher
    ..This review provides an overview of signaling in rolling and adherent neutrophils. ..
  10. Kuwano Y, Spelten O, Zhang H, Ley K, Zarbock A. Rolling on E- or P-selectin induces the extended but not high-affinity conformation of LFA-1 in neutrophils. Blood. 2010;116:617-24 pubmed publisher
    ..We conclude that human neutrophil rolling on E- or P-selectin induces the extended alpha(L)beta(2) integrin conformation through signaling triggered by PSGL-1 engagement. ..
  11. Rotzius P, Thams S, Soehnlein O, Kenne E, Tseng C, Björkström N, et al. Distinct infiltration of neutrophils in lesion shoulders in ApoE-/- mice. Am J Pathol. 2010;177:493-500 pubmed publisher
    ..These data demonstrate neutrophilic granulocytes as a major cellular component of atherosclerotic lesions in ApoE(-/-) mice and call for further study on the roles of these cells in atherogenesis. ..
  12. Simon S, Green C. Molecular mechanics and dynamics of leukocyte recruitment during inflammation. Annu Rev Biomed Eng. 2005;7:151-85 pubmed
    ..New optical tools enable real-time imaging of leukocyte rolling and arrest in parallel plate flow channels (PPFCs), and detection of single-molecule force spectroscopy ..
  13. Pendu R, Terraube V, Christophe O, Gahmberg C, de Groot P, Lenting P, et al. P-selectin glycoprotein ligand 1 and beta2-integrins cooperate in the adhesion of leukocytes to von Willebrand factor. Blood. 2006;108:3746-52 pubmed
    ..VWF is unique in its intrinsic capacity to combine the rolling and the stable adhesion step in the interaction with leukocytes. ..
  14. Harakawa N, Shigeta A, Wato M, Merrill Skoloff G, Furie B, Furie B, et al. P-selectin glycoprotein ligand-1 mediates L-selectin-independent leukocyte rolling in high endothelial venules of peripheral lymph nodes. Int Immunol. 2007;19:321-9 pubmed
    ..To discover whether PSGL-1 plays a role in lymphocyte homing, we examined leukocyte rolling and adhesion in the high endothelial venules (HEVs) of the subiliac LNs of wild-type and PSGL-1-deficient ..
  15. Mueller H, Stadtmann A, Van Aken H, Hirsch E, Wang D, Ley K, et al. Tyrosine kinase Btk regulates E-selectin-mediated integrin activation and neutrophil recruitment by controlling phospholipase C (PLC) gamma2 and PI3Kgamma pathways. Blood. 2010;115:3118-27 pubmed publisher
    Selectins mediate leukocyte rolling, trigger beta(2)-integrin activation, and promote leukocyte recruitment into inflamed tissue...
  16. Spertini C, Baïsse B, Spertini O. Ezrin-radixin-moesin-binding sequence of PSGL-1 glycoprotein regulates leukocyte rolling on selectins and activation of extracellular signal-regulated kinases. J Biol Chem. 2012;287:10693-702 pubmed publisher
  17. Block H, Herter J, Rossaint J, Stadtmann A, Kliche S, Lowell C, et al. Crucial role of SLP-76 and ADAP for neutrophil recruitment in mouse kidney ischemia-reperfusion injury. J Exp Med. 2012;209:407-21 pubmed publisher
    ..degranulation promoting adaptor protein) are involved in E-selectin-mediated integrin activation and slow leukocyte rolling, which promotes ischemia-reperfusion-induced AKI in mice...
  18. Laudanna C, Alon R. Right on the spot. Chemokine triggering of integrin-mediated arrest of rolling leukocytes. Thromb Haemost. 2006;95:5-11 pubmed
  19. Miner J, Xia L, Yago T, Kappelmayer J, Liu Z, Klopocki A, et al. Separable requirements for cytoplasmic domain of PSGL-1 in leukocyte rolling and signaling under flow. Blood. 2008;112:2035-45 pubmed publisher
    ..These data demonstrate that the PSGL-1 cytoplasmic domain is dispensable for leukocyte rolling on P-selectin but is essential to activate beta2 integrins to slow rolling on ICAM-1.
  20. Eriksson E. No detectable endothelial- or leukocyte-derived L-selectin ligand activity on the endothelium in inflamed cremaster muscle venules. J Leukoc Biol. 2008;84:93-103 pubmed publisher
    ..Here, I used intravital microscopy on mouse cremaster muscle venules to show that L-selectin influences leukocyte rolling in inflammation exclusively by mediating L-selectin/PSGL-1-dependent, secondary capture to rolling and ..
  21. Pappu V, Bagchi P. 3D computational modeling and simulation of leukocyte rolling adhesion and deformation. Comput Biol Med. 2008;38:738-53 pubmed publisher
    ..The force loading on individual microvillus and selectin bond is not continuous, rather occurs in steps. Further, we find that the peak force on a tethered microvillus is much higher than that measured to cause tether extrusion. ..
  22. Abbal C, Lambelet M, Bertaggia D, Gerbex C, Martinez M, Arcaro A, et al. Lipid raft adhesion receptors and Syk regulate selectin-dependent rolling under flow conditions. Blood. 2006;108:3352-9 pubmed
    Selectins and their ligand P-selectin glycoprotein ligand-1 (PSGL-1) mediate leukocyte rolling along inflamed vessels...
  23. Sperandio M. Selectins and glycosyltransferases in leukocyte rolling in vivo. FEBS J. 2006;273:4377-89 pubmed
    b>Leukocyte rolling is an important step for the successful recruitment of leukocytes into tissue and occurs predominantly in inflamed microvessels and in high endothelial venules of secondary lymphoid organs...
  24. Rao S, Wang Z, Zuberi R, Sikora L, Bahaie N, Zuraw B, et al. Galectin-3 functions as an adhesion molecule to support eosinophil rolling and adhesion under conditions of flow. J Immunol. 2007;179:7800-7 pubmed
    ..These findings suggest that Gal-3 functions as a cell surface adhesion molecule to support eosinophil rolling and adhesion under conditions of flow. ..
  25. Sundd P, Gutierrez E, Koltsova E, Kuwano Y, Fukuda S, Pospieszalska M, et al. 'Slings' enable neutrophil rolling at high shear. Nature. 2012;488:399-403 pubmed publisher
    ..Each sling effectively lays out a cell-autonomous adhesive substrate in front of neutrophils rolling at high shear stress during inflammation. ..
  26. Ponnuchamy B, Khalil R. Role of ADAMs in endothelial cell permeability: cadherin shedding and leukocyte rolling. Circ Res. 2008;102:1139-42 pubmed publisher
  27. Zarbock A, Abram C, Hundt M, Altman A, Lowell C, Ley K. PSGL-1 engagement by E-selectin signals through Src kinase Fgr and ITAM adapters DAP12 and FcR gamma to induce slow leukocyte rolling. J Exp Med. 2008;205:2339-47 pubmed publisher
  28. Pospieszalska M, Zarbock A, Pickard J, Ley K. Event-tracking model of adhesion identifies load-bearing bonds in rolling leukocytes. Microcirculation. 2009;16:115-30 pubmed publisher
    P-selectin binding to P-selectin glycoprotein ligand-1 (PSGL)-1 mediates leukocyte rolling under conditions of inflammation and injury...
  29. Westmuckett A, Thacker K, Moore K. Tyrosine sulfation of native mouse Psgl-1 is required for optimal leukocyte rolling on P-selectin in vivo. PLoS ONE. 2011;6:e20406 pubmed publisher
    ..Psgl-1 function was assessed by examining P-selectin dependent leukocyte rolling in post-capillary venules of C57BL6 mice transplanted with hematopoietic progenitors from wild type (WT ? B6)..
  30. Rubant S, Ludwig R, Diehl S, Hardt K, Kaufmann R, Pfeilschifter J, et al. Dimethylfumarate reduces leukocyte rolling in vivo through modulation of adhesion molecule expression. J Invest Dermatol. 2008;128:326-31 pubmed
    ..We provide early evidence that DMF affects adhesion molecule expression on human leukocytes and their rolling behavior in vivo, indicating that DMF directly affects the initial step of leukocyte extravasation. ..
  31. Shao B, Yago T, Coghill P, Klopocki A, Mehta D souza P, Schmidtke D, et al. Signal-dependent slow leukocyte rolling does not require cytoskeletal anchorage of P-selectin glycoprotein ligand-1 (PSGL-1) or integrin ?L?2. J Biol Chem. 2012;287:19585-98 pubmed publisher
    ..The cytoskeletal independence of PSGL-1-initiated, ?(L)?(2)-mediated slow rolling differs markedly from the cytoskeletal dependence of chemokine-initiated, ?(L)?(2)-mediated arrest. ..
  32. Sundd P, Gutierrez E, Petrich B, Ginsberg M, Groisman A, Ley K. Live cell imaging of paxillin in rolling neutrophils by dual-color quantitative dynamic footprinting. Microcirculation. 2011;18:361-72 pubmed publisher
    ..Our data suggest that the spectral properties of the fluorochrome do not affect the results. DqDF will be useful for simultaneous visualization of two fluorochromes in the footprint of rolling cells. ..
  33. Yago T, Shao B, Miner J, Yao L, Klopocki A, Maeda K, et al. E-selectin engages PSGL-1 and CD44 through a common signaling pathway to induce integrin alphaLbeta2-mediated slow leukocyte rolling. Blood. 2010;116:485-94 pubmed publisher
    ..Thus, E-selectin triggers common signals through distinct neutrophil glycoproteins to induce alpha(L)beta(2)-dependent slow rolling. ..
  34. Herter J, Rossaint J, Block H, Welch H, Zarbock A. Integrin activation by P-Rex1 is required for selectin-mediated slow leukocyte rolling and intravascular crawling. Blood. 2013;121:2301-10 pubmed publisher
    ..function-associated antigen-1 (LFA-1) extension that corresponds to intermediate affinity and induces slow leukocyte rolling, whereas P-Rex1 is not involved in the induction of the high-affinity conformation of LFA-1 obligatory for ..
  35. Sundd P, Gutierrez E, Pospieszalska M, Zhang H, Groisman A, Ley K. Quantitative dynamic footprinting microscopy reveals mechanisms of neutrophil rolling. Nat Methods. 2010;7:821-4 pubmed publisher
    ..Each rolling neutrophil formed three to four long tethers that extended up to 16 ?m behind the rolling cell. ..
  36. Doyle E, Ridger V, Ferraro F, Turmaine M, Saftig P, Cutler D. CD63 is an essential cofactor to leukocyte recruitment by endothelial P-selectin. Blood. 2011;118:4265-73 pubmed publisher
    ..HUVECs fail to recruit leukocytes, CD63-deficient mice exhibit a significant reduction in both leukocyte rolling and recruitment and we show a failure of leukocyte extravasation in a peritonitis model...
  37. Massena S, Christoffersson G, Hjertström E, Zcharia E, Vlodavsky I, Ausmees N, et al. A chemotactic gradient sequestered on endothelial heparan sulfate induces directional intraluminal crawling of neutrophils. Blood. 2010;116:1924-31 pubmed publisher
    ..In conclusion, an intravascular chemokine gradient sequestered by endothelial HS effectively directs crawling leukocytes toward transmigration loci close to the infection site. ..
  38. Ramos M, Oliveira J, Figueiredo J, Figueiredo I, Kumar V, Bitencourt F, et al. Involvement of NO in the inhibitory effect of Calotropis procera latex protein fractions on leukocyte rolling, adhesion and infiltration in rat peritonitis model. J Ethnopharmacol. 2009;125:387-92 pubmed publisher
  39. Caputo K, Hammer D. Effect of microvillus deformability on leukocyte adhesion explored using adhesive dynamics simulations. Biophys J. 2005;89:187-200 pubmed
    b>Leukocyte rolling on the endothelium via selectin molecules is an important step in the adhesion cascade, which allows leukocytes in the bloodstream to reach sites of infection...
  40. McEver R. A sulfated address for lymphocyte homing. Nat Immunol. 2005;6:1067-9 pubmed
  41. Frommhold D, Mannigel I, Schymeinsky J, Mocsai A, Poeschl J, Walzog B, et al. Spleen tyrosine kinase Syk is critical for sustained leukocyte adhesion during inflammation in vivo. BMC Immunol. 2007;8:31 pubmed
    ..We provide substantial evidence for an important role of Syk in mediating beta2-integrin dependent outside-in signaling leading to sustained leukocyte adhesion and spreading during the inflammatory response in vivo. ..
  42. Dal Secco D, Moreira A, Freitas A, Silva J, Rossi M, Ferreira S, et al. Nitric oxide inhibits neutrophil migration by a mechanism dependent on ICAM-1: role of soluble guanylate cyclase. Nitric Oxide. 2006;15:77-86 pubmed
    ..Moreover, these NO effects are mediated via cGMP. ..
  43. Zarbock A, Lowell C, Ley K. Spleen tyrosine kinase Syk is necessary for E-selectin-induced alpha(L)beta(2) integrin-mediated rolling on intercellular adhesion molecule-1. Immunity. 2007;26:773-83 pubmed
    ..This identifies a second neutrophil-activation pathway that is as important as activation through G protein-coupled receptors (GPCRs). ..
  44. Tang J, Hunt C. Identifying the rules of engagement enabling leukocyte rolling, activation, and adhesion. PLoS Comput Biol. 2010;6:e1000681 pubmed publisher
    ..as a concrete, working theory about detailed events occurring at the leukocyte-surface interface during leukocyte rolling and adhesion experiments...
  45. Dole V, Bergmeier W, Mitchell H, Eichenberger S, Wagner D. Activated platelets induce Weibel-Palade-body secretion and leukocyte rolling in vivo: role of P-selectin. Blood. 2005;106:2334-9 pubmed
    ..the formation of transient platelet-leukocyte aggregates and resulted in a several-fold systemic increase in leukocyte rolling 2 to 4 hours after infusion. Rolling returned to baseline levels 7 hours after infusion...
  46. Sumagin R, Kuebel J, Sarelius I. Leukocyte rolling and adhesion both contribute to regulation of microvascular permeability to albumin via ligation of ICAM-1. Am J Physiol Cell Physiol. 2011;301:C804-13 pubmed publisher
    ..Use of function-blocking antibodies to separately block leukocyte rolling or adhesion under unstimulated or TNF-?-activated conditions established that both rolling and adhered ..
  47. Rao R, Yang L, Garcia Cardena G, Luscinskas F. Endothelial-dependent mechanisms of leukocyte recruitment to the vascular wall. Circ Res. 2007;101:234-47 pubmed
  48. Menezes M, Paes Leme A, Melo R, Silva C, Della Casa M, Bruni F, et al. Activation of leukocyte rolling by the cysteine-rich domain and the hyper-variable region of HF3, a snake venom hemorrhagic metalloproteinase. FEBS Lett. 2008;582:3915-21 pubmed publisher
    ..and cysteine-rich proteins) but not the disintegrin-like protein were able to significantly increase leukocyte rolling in the microcirculation...
  49. Caputo K, Hammer D. Adhesive dynamics simulation of G-protein-mediated chemokine-activated neutrophil adhesion. Biophys J. 2009;96:2989-3004 pubmed publisher
  50. Stadtmann A, Brinkhaus L, Mueller H, Rossaint J, Bolomini Vittori M, Bergmeier W, et al. Rap1a activation by CalDAG-GEFI and p38 MAPK is involved in E-selectin-dependent slow leukocyte rolling. Eur J Immunol. 2011;41:2074-85 pubmed publisher
    ..Our data demonstrate that Rap1a activation by p38 MAPK and CalDAG-GEFI is involved in E-selectin-dependent slow rolling and leukocyte recruitment. ..
  51. Alvarez A, Cerda Nicolas M, Naim Abu Nabah Y, Mata M, Issekutz A, Panes J, et al. Direct evidence of leukocyte adhesion in arterioles by angiotensin II. Blood. 2004;104:402-8 pubmed
    ..Therefore, Ang II may be a key molecule in cardiovascular diseases in which leukocyte adhesion to the arteries is a characteristic feature. ..
  52. Setiadi H, McEver R. Signal-dependent distribution of cell surface P-selectin in clathrin-coated pits affects leukocyte rolling under flow. J Cell Biol. 2003;163:1385-95 pubmed
    ..it is internalized, P-selectin clusters in clathrin-coated pits, which enhances its ability to support leukocyte rolling. We found that thrombin and histamine induced comparable exocytosis of P-selectin on endothelial cells...
  53. Hicks A, Nolan S, Ridger V, Hellewell P, Norman K. Recombinant P-selectin glycoprotein ligand-1 directly inhibits leukocyte rolling by all 3 selectins in vivo: complete inhibition of rolling is not required for anti-inflammatory effect. Blood. 2003;101:3249-56 pubmed
    Selectin-dependent leukocyte rolling is one of the earliest steps of an acute inflammatory response and, as such, contributes to many inflammatory diseases...