Abstract
In postcapillary venules, marginating neutrophils (PMNs) are often seen rolling along the vessel wall prior to stopping and emigrating. There is substantial evidence in vitro and in vivo that the adhesion receptors E- and L-selectin participate in this phenomenon on cytokine-stimulated endothelium, and recent evidence has shown that a closely related adhesion receptor, P-selectin, is capable of mediating neutrophil rolling on an artificial membrane. Here we demonstrate and characterize PMN rolling on monolayers of human umbilical vein endothelial cells (HUVECs) stimulated with histamine to induce surface expression of P-selectin. Peak association of PMNs with the HUVECs occurs 10 min after histamine stimulation, and at a postcapillary venular wall shear stress of 2.0 dyn/cm2 the rolling velocity is 14 microns/s. Approximately 95% of the PMNs roll on the endothelial cells, 5% adhere firmly, and none migrate beneath the endothelial monolayer. Monoclonal antibody (MAb) G1, which binds P-selectin and blocks its adhesive function, completely prevents association of the PMNs with histamine-stimulated HUVEC, whereas the nonblocking anti-P-selectin MAb S12 does not. Treatment of PMNs with the anti-L-selectin MAb DREG56 reduces PMN adherence by approximately 50%. Anti-CD54 MAb R6.5 and anti-CD18 MAb R15.7 have little effect on the number of PMNs rolling on the HUVECs but completely prevent PMNs from stopping and significantly increase rolling velocity. Nonblocking control MAbs for R6.5 (CL203) and R15.7 (CL18/1D1) lack these effects. Rolling adhesion of PMNs on histamine-stimulated HUVECs therefore appears to be completely dependent on endothelial cell P-selectin, with a minor adhesion-stabilizing contribution from intercellular adhesion molecule 1 and beta 2 integrins. The partial inhibition of rolling with DREG56 suggests that L-selectin may also play a role in neutrophil interactions with histamine-stimulated endothelium. We further characterize these interactions by determining the effects of the various MAbs and wall shear stresses on adhesion patterns, rolling velocities, and distributions of rolling velocities.
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Selected References
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- Abbassi O., Lane C. L., Krater S., Kishimoto T. K., Anderson D. C., McIntire L. V., Smith C. W. Canine neutrophil margination mediated by lectin adhesion molecule-1 in vitro. J Immunol. 1991 Oct 1;147(7):2107–2115. [PubMed] [Google Scholar]
- Arfors K. E., Lundberg C., Lindbom L., Lundberg K., Beatty P. G., Harlan J. M. A monoclonal antibody to the membrane glycoprotein complex CD18 inhibits polymorphonuclear leukocyte accumulation and plasma leakage in vivo. Blood. 1987 Jan;69(1):338–340. [PubMed] [Google Scholar]
- Atherton A., Born G. V. Quantitative investigations of the adhesiveness of circulating polymorphonuclear leucocytes to blood vessel walls. J Physiol. 1972 Apr;222(2):447–474. doi: 10.1113/jphysiol.1972.sp009808. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Atherton A., Born G. V. Relationship between the velocity of rolling granulocytes and that of the blood flow in venules. J Physiol. 1973 Aug;233(1):157–165. doi: 10.1113/jphysiol.1973.sp010303. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bevilacqua M. P., Pober J. S., Mendrick D. L., Cotran R. S., Gimbrone M. A., Jr Identification of an inducible endothelial-leukocyte adhesion molecule. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9238–9242. doi: 10.1073/pnas.84.24.9238. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chien S. Rheology in the microcirculation in normal and low flow states. Adv Shock Res. 1982;8:71–80. [PubMed] [Google Scholar]
- Diamond M. S., Staunton D. E., de Fougerolles A. R., Stacker S. A., Garcia-Aguilar J., Hibbs M. L., Springer T. A. ICAM-1 (CD54): a counter-receptor for Mac-1 (CD11b/CD18). J Cell Biol. 1990 Dec;111(6 Pt 2):3129–3139. doi: 10.1083/jcb.111.6.3129. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dustin M. L., Springer T. A. Lymphocyte function-associated antigen-1 (LFA-1) interaction with intercellular adhesion molecule-1 (ICAM-1) is one of at least three mechanisms for lymphocyte adhesion to cultured endothelial cells. J Cell Biol. 1988 Jul;107(1):321–331. doi: 10.1083/jcb.107.1.321. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Entman M. L., Youker K., Shappell S. B., Siegel C., Rothlein R., Dreyer W. J., Schmalstieg F. C., Smith C. W. Neutrophil adherence to isolated adult canine myocytes. Evidence for a CD18-dependent mechanism. J Clin Invest. 1990 May;85(5):1497–1506. doi: 10.1172/JCI114596. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gamble J. R., Skinner M. P., Berndt M. C., Vadas M. A. Prevention of activated neutrophil adhesion to endothelium by soluble adhesion protein GMP140. Science. 1990 Jul 27;249(4967):414–417. doi: 10.1126/science.1696029. [DOI] [PubMed] [Google Scholar]
- Geng J. G., Bevilacqua M. P., Moore K. L., McIntyre T. M., Prescott S. M., Kim J. M., Bliss G. A., Zimmerman G. A., McEver R. P. Rapid neutrophil adhesion to activated endothelium mediated by GMP-140. Nature. 1990 Feb 22;343(6260):757–760. doi: 10.1038/343757a0. [DOI] [PubMed] [Google Scholar]
- Hammer D. A., Apte S. M. Simulation of cell rolling and adhesion on surfaces in shear flow: general results and analysis of selectin-mediated neutrophil adhesion. Biophys J. 1992 Jul;63(1):35–57. doi: 10.1016/S0006-3495(92)81577-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hattori R., Hamilton K. K., Fugate R. D., McEver R. P., Sims P. J. Stimulated secretion of endothelial von Willebrand factor is accompanied by rapid redistribution to the cell surface of the intracellular granule membrane protein GMP-140. J Biol Chem. 1989 May 15;264(14):7768–7771. [PubMed] [Google Scholar]
- Hogg N., Bennett R., Cabañas C., Dransfield I. Leukocyte integrin activation. Kidney Int. 1992 Mar;41(3):613–616. doi: 10.1038/ki.1992.93. [DOI] [PubMed] [Google Scholar]
- Huber A. R., Kunkel S. L., Todd R. F., 3rd, Weiss S. J. Regulation of transendothelial neutrophil migration by endogenous interleukin-8. Science. 1991 Oct 4;254(5028):99–102. doi: 10.1126/science.1718038. [DOI] [PubMed] [Google Scholar]
- Hughes B. J., Hollers J. C., Crockett-Torabi E., Smith C. W. Recruitment of CD11b/CD18 to the neutrophil surface and adherence-dependent cell locomotion. J Clin Invest. 1992 Nov;90(5):1687–1696. doi: 10.1172/JCI116041. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Juliano R. L., Haskill S. Signal transduction from the extracellular matrix. J Cell Biol. 1993 Feb;120(3):577–585. doi: 10.1083/jcb.120.3.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jutila M. A., Rott L., Berg E. L., Butcher E. C. Function and regulation of the neutrophil MEL-14 antigen in vivo: comparison with LFA-1 and MAC-1. J Immunol. 1989 Nov 15;143(10):3318–3324. [PubMed] [Google Scholar]
- Kishimoto T. K., Jutila M. A., Berg E. L., Butcher E. C. Neutrophil Mac-1 and MEL-14 adhesion proteins inversely regulated by chemotactic factors. Science. 1989 Sep 15;245(4923):1238–1241. doi: 10.1126/science.2551036. [DOI] [PubMed] [Google Scholar]
- Kishimoto T. K., Jutila M. A., Butcher E. C. Identification of a human peripheral lymph node homing receptor: a rapidly down-regulated adhesion molecule. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2244–2248. doi: 10.1073/pnas.87.6.2244. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kishimoto T. K., Warnock R. A., Jutila M. A., Butcher E. C., Lane C., Anderson D. C., Smith C. W. Antibodies against human neutrophil LECAM-1 (LAM-1/Leu-8/DREG-56 antigen) and endothelial cell ELAM-1 inhibit a common CD18-independent adhesion pathway in vitro. Blood. 1991 Aug 1;78(3):805–811. [PubMed] [Google Scholar]
- Kuijpers T. W., Hakkert B. C., Hart M. H., Roos D. Neutrophil migration across monolayers of cytokine-prestimulated endothelial cells: a role for platelet-activating factor and IL-8. J Cell Biol. 1992 May;117(3):565–572. doi: 10.1083/jcb.117.3.565. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lasky L. A. Selectins: interpreters of cell-specific carbohydrate information during inflammation. Science. 1992 Nov 6;258(5084):964–969. doi: 10.1126/science.1439808. [DOI] [PubMed] [Google Scholar]
- Lawrence M. B., McIntire L. V., Eskin S. G. Effect of flow on polymorphonuclear leukocyte/endothelial cell adhesion. Blood. 1987 Nov;70(5):1284–1290. [PubMed] [Google Scholar]
- Lawrence M. B., Smith C. W., Eskin S. G., McIntire L. V. Effect of venous shear stress on CD18-mediated neutrophil adhesion to cultured endothelium. Blood. 1990 Jan 1;75(1):227–237. [PubMed] [Google Scholar]
- Lawrence M. B., Springer T. A. Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. Cell. 1991 May 31;65(5):859–873. doi: 10.1016/0092-8674(91)90393-d. [DOI] [PubMed] [Google Scholar]
- Lewis M. S., Whatley R. E., Cain P., McIntyre T. M., Prescott S. M., Zimmerman G. A. Hydrogen peroxide stimulates the synthesis of platelet-activating factor by endothelium and induces endothelial cell-dependent neutrophil adhesion. J Clin Invest. 1988 Dec;82(6):2045–2055. doi: 10.1172/JCI113825. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ley K., Gaehtgens P., Fennie C., Singer M. S., Lasky L. A., Rosen S. D. Lectin-like cell adhesion molecule 1 mediates leukocyte rolling in mesenteric venules in vivo. Blood. 1991 Jun 15;77(12):2553–2555. [PubMed] [Google Scholar]
- Lorant D. E., Patel K. D., McIntyre T. M., McEver R. P., Prescott S. M., Zimmerman G. A. Coexpression of GMP-140 and PAF by endothelium stimulated by histamine or thrombin: a juxtacrine system for adhesion and activation of neutrophils. J Cell Biol. 1991 Oct;115(1):223–234. doi: 10.1083/jcb.115.1.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lorant D. E., Topham M. K., Whatley R. E., McEver R. P., McIntyre T. M., Prescott S. M., Zimmerman G. A. Inflammatory roles of P-selectin. J Clin Invest. 1993 Aug;92(2):559–570. doi: 10.1172/JCI116623. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McEver R. P., Martin M. N. A monoclonal antibody to a membrane glycoprotein binds only to activated platelets. J Biol Chem. 1984 Aug 10;259(15):9799–9804. [PubMed] [Google Scholar]
- McEver R. P. Selectins: novel receptors that mediate leukocyte adhesion during inflammation. Thromb Haemost. 1991 Mar 4;65(3):223–228. [PubMed] [Google Scholar]
- Moore K. L., Stults N. L., Diaz S., Smith D. F., Cummings R. D., Varki A., McEver R. P. Identification of a specific glycoprotein ligand for P-selectin (CD62) on myeloid cells. J Cell Biol. 1992 Jul;118(2):445–456. doi: 10.1083/jcb.118.2.445. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Norgard K. E., Moore K. L., Diaz S., Stults N. L., Ushiyama S., McEver R. P., Cummings R. D., Varki A. Characterization of a specific ligand for P-selectin on myeloid cells. A minor glycoprotein with sialylated O-linked oligosaccharides. J Biol Chem. 1993 Jun 15;268(17):12764–12774. [PubMed] [Google Scholar]
- Osborn L., Hession C., Tizard R., Vassallo C., Luhowskyj S., Chi-Rosso G., Lobb R. Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes. Cell. 1989 Dec 22;59(6):1203–1211. doi: 10.1016/0092-8674(89)90775-7. [DOI] [PubMed] [Google Scholar]
- Patel K. D., Zimmerman G. A., Prescott S. M., McEver R. P., McIntyre T. M. Oxygen radicals induce human endothelial cells to express GMP-140 and bind neutrophils. J Cell Biol. 1991 Feb;112(4):749–759. doi: 10.1083/jcb.112.4.749. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Perry M. A., Granger D. N. Role of CD11/CD18 in shear rate-dependent leukocyte-endothelial cell interactions in cat mesenteric venules. J Clin Invest. 1991 May;87(5):1798–1804. doi: 10.1172/JCI115200. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Picker L. J., Warnock R. A., Burns A. R., Doerschuk C. M., Berg E. L., Butcher E. C. The neutrophil selectin LECAM-1 presents carbohydrate ligands to the vascular selectins ELAM-1 and GMP-140. Cell. 1991 Sep 6;66(5):921–933. doi: 10.1016/0092-8674(91)90438-5. [DOI] [PubMed] [Google Scholar]
- Pober J. S., Gimbrone M. A., Jr, Lapierre L. A., Mendrick D. L., Fiers W., Rothlein R., Springer T. A. Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor, and immune interferon. J Immunol. 1986 Sep 15;137(6):1893–1896. [PubMed] [Google Scholar]
- Prescott S. M., Zimmerman G. A., McIntyre T. M. Human endothelial cells in culture produce platelet-activating factor (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) when stimulated with thrombin. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3534–3538. doi: 10.1073/pnas.81.11.3534. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schmid-Schönbein G. W., Engler R. L. Perspectives of leukocyte activation in the microcirculation. Biorheology. 1990;27(6):859–869. doi: 10.3233/bir-1990-27606. [DOI] [PubMed] [Google Scholar]
- Smith C. W., Entman M. L., Lane C. L., Beaudet A. L., Ty T. I., Youker K., Hawkins H. K., Anderson D. C. Adherence of neutrophils to canine cardiac myocytes in vitro is dependent on intercellular adhesion molecule-1. J Clin Invest. 1991 Oct;88(4):1216–1223. doi: 10.1172/JCI115424. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith C. W., Kishimoto T. K., Abbassi O., Hughes B., Rothlein R., McIntire L. V., Butcher E., Anderson D. C., Abbass O. Chemotactic factors regulate lectin adhesion molecule 1 (LECAM-1)-dependent neutrophil adhesion to cytokine-stimulated endothelial cells in vitro. J Clin Invest. 1991 Feb;87(2):609–618. doi: 10.1172/JCI115037. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith C. W., Rothlein R., Hughes B. J., Mariscalco M. M., Rudloff H. E., Schmalstieg F. C., Anderson D. C. Recognition of an endothelial determinant for CD 18-dependent human neutrophil adherence and transendothelial migration. J Clin Invest. 1988 Nov;82(5):1746–1756. doi: 10.1172/JCI113788. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith W. B., Gamble J. R., Clark-Lewis I., Vadas M. A. Interleukin-8 induces neutrophil transendothelial migration. Immunology. 1991 Jan;72(1):65–72. [PMC free article] [PubMed] [Google Scholar]
- Sugama Y., Tiruppathi C., offakidevi K., Andersen T. T., Fenton J. W., 2nd, Malik A. B. Thrombin-induced expression of endothelial P-selectin and intercellular adhesion molecule-1: a mechanism for stabilizing neutrophil adhesion. J Cell Biol. 1992 Nov;119(4):935–944. doi: 10.1083/jcb.119.4.935. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tözeren A., Ley K. How do selectins mediate leukocyte rolling in venules? Biophys J. 1992 Sep;63(3):700–709. doi: 10.1016/S0006-3495(92)81660-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Von Andrian U. H., Hansell P., Chambers J. D., Berger E. M., Torres Filho I., Butcher E. C., Arfors K. E. L-selectin function is required for beta 2-integrin-mediated neutrophil adhesion at physiological shear rates in vivo. Am J Physiol. 1992 Oct;263(4 Pt 2):H1034–H1044. doi: 10.1152/ajpheart.1992.263.4.H1034. [DOI] [PubMed] [Google Scholar]
- Wong C. S., Gamble J. R., Skinner M. P., Lucas C. M., Berndt M. C., Vadas M. A. Adhesion protein GMP140 inhibits superoxide anion release by human neutrophils. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2397–2401. doi: 10.1073/pnas.88.6.2397. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zimmerman G. A., McIntyre T. M., Mehra M., Prescott S. M. Endothelial cell-associated platelet-activating factor: a novel mechanism for signaling intercellular adhesion. J Cell Biol. 1990 Feb;110(2):529–540. doi: 10.1083/jcb.110.2.529. [DOI] [PMC free article] [PubMed] [Google Scholar]
- von Andrian U. H., Chambers J. D., McEvoy L. M., Bargatze R. F., Arfors K. E., Butcher E. C. Two-step model of leukocyte-endothelial cell interaction in inflammation: distinct roles for LECAM-1 and the leukocyte beta 2 integrins in vivo. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7538–7542. doi: 10.1073/pnas.88.17.7538. [DOI] [PMC free article] [PubMed] [Google Scholar]