Skip to main content
PMC home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1992 May 1;117(3):565–572. doi: 10.1083/jcb.117.3.565

Neutrophil migration across monolayers of cytokine-prestimulated endothelial cells: a role for platelet-activating factor and IL-8

PMCID: PMC2289445  PMID: 1315317

Abstract

In a previous study we observed that neutrophils respond with a rapid rise in [Ca2+]i during adherence to cytokine-activated endothelial cells (EC), caused by EC membrane-associated platelet-activating factor (PAF). In the present study, we investigated whether this form of PAF was important in neutrophil adherence and migration across monolayers of rIL-1 beta- or rTNF alpha-prestimulated EC. PAF receptor antagonists prevented neutrophil migration across cytokine-pretreated EC by approximately 60% (P less than 0.005) without interfering with the process of adherence. The antagonists WEB 2086 and L-652,731 had no effect on neutrophil migration across resting EC induced by formylmethionyl-leucyl-phenylalanine (FMLP). A murine anti-IL-8 antiserum was found to also partially inhibit the neutrophil transmigration across cytokine-activated EC. When the anti-IL-8 antiserum was used in combination with a PAF receptor antagonist, neutrophil migration across cytokine-pretreated monolayers of EC was completely prevented. During transmigration, LAM-1 and CD44 on the neutrophils were down-modulated; both WEB 2086 and anti-IL-8 antiserum partially prevented this down-modulation caused by cytokine- prestimulated EC. Our results indicate that human neutrophils are activated and guided by EC-associated PAF and EC-derived IL-8 during the in vitro diapedesis in between cytokine-stimulated EC.

Full Text

The Full Text of this article is available as a PDF (931.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson D. C., Schmalsteig F. C., Finegold M. J., Hughes B. J., Rothlein R., Miller L. J., Kohl S., Tosi M. F., Jacobs R. L., Waldrop T. C. The severe and moderate phenotypes of heritable Mac-1, LFA-1 deficiency: their quantitative definition and relation to leukocyte dysfunction and clinical features. J Infect Dis. 1985 Oct;152(4):668–689. doi: 10.1093/infdis/152.4.668. [DOI] [PubMed] [Google Scholar]
  2. Aruffo A., Stamenkovic I., Melnick M., Underhill C. B., Seed B. CD44 is the principal cell surface receptor for hyaluronate. Cell. 1990 Jun 29;61(7):1303–1313. doi: 10.1016/0092-8674(90)90694-a. [DOI] [PubMed] [Google Scholar]
  3. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  4. Baggiolini M., Walz A., Kunkel S. L. Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest. 1989 Oct;84(4):1045–1049. doi: 10.1172/JCI114265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Benveniste J., Henson P. M., Cochrane C. G. Leukocyte-dependent histamine release from rabbit platelets. The role of IgE, basophils, and a platelet-activating factor. J Exp Med. 1972 Dec 1;136(6):1356–1377. doi: 10.1084/jem.136.6.1356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Bevilacqua M. P., Stengelin S., Gimbrone M. A., Jr, Seed B. Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science. 1989 Mar 3;243(4895):1160–1165. doi: 10.1126/science.2466335. [DOI] [PubMed] [Google Scholar]
  8. Breviario F., Bertocchi F., Dejana E., Bussolino F. IL-1-induced adhesion of polymorphonuclear leukocytes to cultured human endothelial cells. Role of platelet-activating factor. J Immunol. 1988 Nov 15;141(10):3391–3397. [PubMed] [Google Scholar]
  9. Bussolino F., Breviario F., Tetta C., Aglietta M., Mantovani A., Dejana E. Interleukin 1 stimulates platelet-activating factor production in cultured human endothelial cells. J Clin Invest. 1986 Jun;77(6):2027–2033. doi: 10.1172/JCI112532. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Camerini D., James S. P., Stamenkovic I., Seed B. Leu-8/TQ1 is the human equivalent of the Mel-14 lymph node homing receptor. Nature. 1989 Nov 2;342(6245):78–82. doi: 10.1038/342078a0. [DOI] [PubMed] [Google Scholar]
  11. Dent G., Ukena D., Chanez P., Sybrecht G., Barnes P. Characterization of PAF receptors on human neutrophils using the specific antagonist, WEB 2086. Correlation between receptor binding and function. FEBS Lett. 1989 Feb 27;244(2):365–368. doi: 10.1016/0014-5793(89)80564-2. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Dustin M. L., Rothlein R., Bhan A. K., Dinarello C. A., Springer T. A. Induction by IL 1 and interferon-gamma: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). J Immunol. 1986 Jul 1;137(1):245–254. [PubMed] [Google Scholar]
  14. Furie M. B., Cramer E. B., Naprstek B. L., Silverstein S. C. Cultured endothelial cell monolayers that restrict the transendothelial passage of macromolecules and electrical current. J Cell Biol. 1984 Mar;98(3):1033–1041. doi: 10.1083/jcb.98.3.1033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Furie M. B., McHugh D. D. Migration of neutrophils across endothelial monolayers is stimulated by treatment of the monolayers with interleukin-1 or tumor necrosis factor-alpha. J Immunol. 1989 Nov 15;143(10):3309–3317. [PubMed] [Google Scholar]
  16. 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]
  17. 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]
  18. Gimbrone M. A., Jr, Obin M. S., Brock A. F., Luis E. A., Hass P. E., Hébert C. A., Yip Y. K., Leung D. W., Lowe D. G., Kohr W. J. Endothelial interleukin-8: a novel inhibitor of leukocyte-endothelial interactions. Science. 1989 Dec 22;246(4937):1601–1603. doi: 10.1126/science.2688092. [DOI] [PubMed] [Google Scholar]
  19. Hakkert B. C., Kuijpers T. W., Leeuwenberg J. F., van Mourik J. A., Roos D. Neutrophil and monocyte adherence to and migration across monolayers of cytokine-activated endothelial cells: the contribution of CD18, ELAM-1, and VLA-4. Blood. 1991 Nov 15;78(10):2721–2726. [PubMed] [Google Scholar]
  20. Hakkert B. C., Rentenaar J. M., Van Aken W. G., Roos D., Van Mourik J. A. A three-dimensional model system to study the interactions between human leukocytes and endothelial cells. Eur J Immunol. 1990 Dec;20(12):2775–2781. doi: 10.1002/eji.1830201236. [DOI] [PubMed] [Google Scholar]
  21. Harlan J. M. Leukocyte-endothelial interactions. Blood. 1985 Mar;65(3):513–525. [PubMed] [Google Scholar]
  22. Haynes B. F., Telen M. J., Hale L. P., Denning S. M. CD44--a molecule involved in leukocyte adherence and T-cell activation. Immunol Today. 1989 Dec;10(12):423–428. doi: 10.1016/0167-5699(89)90040-6. [DOI] [PubMed] [Google Scholar]
  23. Honda Z., Nakamura M., Miki I., Minami M., Watanabe T., Seyama Y., Okado H., Toh H., Ito K., Miyamoto T. Cloning by functional expression of platelet-activating factor receptor from guinea-pig lung. Nature. 1991 Jan 24;349(6307):342–346. doi: 10.1038/349342a0. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Hwang S. B., Lam M. H., Biftu T., Beattie T. R., Shen T. Y. trans-2,5-Bis-(3,4,5-trimethoxyphenyl)tetrahydrofuran. An orally active specific and competitive receptor antagonist of platelet activating factor. J Biol Chem. 1985 Dec 15;260(29):15639–15645. [PubMed] [Google Scholar]
  26. Jaffe E. A., Nachman R. L., Becker C. G., Minick C. R. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest. 1973 Nov;52(11):2745–2756. doi: 10.1172/JCI107470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Johnston G. I., Cook R. G., McEver R. P. Cloning of GMP-140, a granule membrane protein of platelets and endothelium: sequence similarity to proteins involved in cell adhesion and inflammation. Cell. 1989 Mar 24;56(6):1033–1044. doi: 10.1016/0092-8674(89)90636-3. [DOI] [PubMed] [Google Scholar]
  28. Jutila M. A., Kishimoto T. K., Butcher E. C. Regulation and lectin activity of the human neutrophil peripheral lymph node homing receptor. Blood. 1990 Jul 1;76(1):178–183. [PubMed] [Google Scholar]
  29. 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]
  30. Kansas G. S., Wood G. S., Fishwild D. M., Engleman E. G. Functional characterization of human T lymphocyte subsets distinguished by monoclonal anti-leu-8. J Immunol. 1985 May;134(5):2995–3002. [PubMed] [Google Scholar]
  31. Kuijpers T. W., Hakkert B. C., Hoogerwerf M., Leeuwenberg J. F., Roos D. Role of endothelial leukocyte adhesion molecule-1 and platelet-activating factor in neutrophil adherence to IL-1-prestimulated endothelial cells. Endothelial leukocyte adhesion molecule-1-mediated CD18 activation. J Immunol. 1991 Aug 15;147(4):1369–1376. [PubMed] [Google Scholar]
  32. Kuijpers T. W., Hoogerwerf M., Roos D. Neutrophil migration across monolayers of resting or cytokine-activated endothelial cells. Role of intracellular calcium changes and fusion of specific granules with the plasma membrane. J Immunol. 1992 Jan 1;148(1):72–77. [PubMed] [Google Scholar]
  33. Kuijpers T. W., Tool A. T., van der Schoot C. E., Ginsel L. A., Onderwater J. J., Roos D., Verhoeven A. J. Membrane surface antigen expression on neutrophils: a reappraisal of the use of surface markers for neutrophil activation. Blood. 1991 Aug 15;78(4):1105–1111. [PubMed] [Google Scholar]
  34. Kuypers T. W., Roos D. Leukocyte membrane adhesion proteins LFA-1, CR3 and p150,95: a review of functional and regulatory aspects. Res Immunol. 1989 Jun-Aug;140(5-6):461–486. doi: 10.1016/0923-2494(89)90114-4. [DOI] [PubMed] [Google Scholar]
  35. Leeuwenberg J. F., Jeunhomme T. M., Buurman W. A. Induction of an activation antigen on human endothelial cells in vitro. Eur J Immunol. 1989 Apr;19(4):715–720. doi: 10.1002/eji.1830190422. [DOI] [PubMed] [Google Scholar]
  36. 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]
  37. Luscinskas F. W., Brock A. F., Arnaout M. A., Gimbrone M. A., Jr Endothelial-leukocyte adhesion molecule-1-dependent and leukocyte (CD11/CD18)-dependent mechanisms contribute to polymorphonuclear leukocyte adhesion to cytokine-activated human vascular endothelium. J Immunol. 1989 Apr 1;142(7):2257–2263. [PubMed] [Google Scholar]
  38. Miedema F., Tetteroo P. A., Hesselink W. G., Werner G., Spits H., Melief C. J. Both Fc receptors and lymphocyte-function-associated antigen 1 on human T gamma lymphocytes are required for antibody-dependent cellular cytotoxicity (killer cell activity). Eur J Immunol. 1984 Jun;14(6):518–523. doi: 10.1002/eji.1830140607. [DOI] [PubMed] [Google Scholar]
  39. Miyake K., Underhill C. B., Lesley J., Kincade P. W. Hyaluronate can function as a cell adhesion molecule and CD44 participates in hyaluronate recognition. J Exp Med. 1990 Jul 1;172(1):69–75. doi: 10.1084/jem.172.1.69. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Moser R., Schleiffenbaum B., Groscurth P., Fehr J. Interleukin 1 and tumor necrosis factor stimulate human vascular endothelial cells to promote transendothelial neutrophil passage. J Clin Invest. 1989 Feb;83(2):444–455. doi: 10.1172/JCI113903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Pals S. T., Hogervorst F., Keizer G. D., Thepen T., Horst E., Figdor C. C. Identification of a widely distributed 90-kDa glycoprotein that is homologous to the Hermes-1 human lymphocyte homing receptor. J Immunol. 1989 Aug 1;143(3):851–857. [PubMed] [Google Scholar]
  42. Prescott S. M., Zimmerman G. A., McIntyre T. M. Platelet-activating factor. J Biol Chem. 1990 Oct 15;265(29):17381–17384. [PubMed] [Google Scholar]
  43. Remy E., Lenoir G., Houben A., Vandesteene C., Remacle J. Inhibition of platelet-activating factor biosynthesis via the acetyltransferase by arachidonic and oleic acids in ionophore A23187-stimulated bovine neutrophils. Biochim Biophys Acta. 1989 Sep 11;1005(1):87–92. doi: 10.1016/0005-2760(89)90035-0. [DOI] [PubMed] [Google Scholar]
  44. Roos D., de Boer M. Purification and cryopreservation of phagocytes from human blood. Methods Enzymol. 1986;132:225–243. doi: 10.1016/s0076-6879(86)32010-x. [DOI] [PubMed] [Google Scholar]
  45. Rosenfeld S. I., Looney R. J., Leddy J. P., Phipps D. C., Abraham G. N., Anderson C. L. Human platelet Fc receptor for immunoglobulin G. Identification as a 40,000-molecular-weight membrane protein shared by monocytes. J Clin Invest. 1985 Dec;76(6):2317–2322. doi: 10.1172/JCI112242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Rothlein R., Dustin M. L., Marlin S. D., Springer T. A. A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1. J Immunol. 1986 Aug 15;137(4):1270–1274. [PubMed] [Google Scholar]
  47. Schröder J. M., Christophers E. Secretion of novel and homologous neutrophil-activating peptides by LPS-stimulated human endothelial cells. J Immunol. 1989 Jan 1;142(1):244–251. [PubMed] [Google Scholar]
  48. 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]
  49. Springer T. A. Adhesion receptors of the immune system. Nature. 1990 Aug 2;346(6283):425–434. doi: 10.1038/346425a0. [DOI] [PubMed] [Google Scholar]
  50. Tedder T. F., Isaacs C. M., Ernst T. J., Demetri G. D., Adler D. A., Disteche C. M. Isolation and chromosomal localization of cDNAs encoding a novel human lymphocyte cell surface molecule, LAM-1. Homology with the mouse lymphocyte homing receptor and other human adhesion proteins. J Exp Med. 1989 Jul 1;170(1):123–133. doi: 10.1084/jem.170.1.123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Watson S. R., Fennie C., Lasky L. A. Neutrophil influx into an inflammatory site inhibited by a soluble homing receptor-IgG chimaera. Nature. 1991 Jan 10;349(6305):164–167. doi: 10.1038/349164a0. [DOI] [PubMed] [Google Scholar]
  52. Wheeler M. E., Luscinskas F. W., Bevilacqua M. P., Gimbrone M. A., Jr Cultured human endothelial cells stimulated with cytokines or endotoxin produce an inhibitor of leukocyte adhesion. J Clin Invest. 1988 Oct;82(4):1211–1218. doi: 10.1172/JCI113718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Willems C., Astaldi G. C., De Groot P. G., Janssen M. C., Gonsalvez M. D., Zeijlemaker W. P., Van Mourik J. A., Van Aken W. G. Media conditioned by cultured human vascular endothelial cells inhibit the growth of vascular smooth muscle cells. Exp Cell Res. 1982 May;139(1):191–197. doi: 10.1016/0014-4827(82)90332-9. [DOI] [PubMed] [Google Scholar]
  54. Williams K. I., Higgs G. A. Eicosanoids and inflammation. J Pathol. 1988 Oct;156(2):101–110. doi: 10.1002/path.1711560204. [DOI] [PubMed] [Google Scholar]
  55. Zavoico G. B., Ewenstein B. M., Schafer A. I., Pober J. S. IL-1 and related cytokines enhance thrombin-stimulated PGI2 production in cultured endothelial cells without affecting thrombin-stimulated von Willebrand factor secretion or platelet-activating factor biosynthesis. J Immunol. 1989 Jun 1;142(11):3993–3999. [PubMed] [Google Scholar]
  56. van der Reijden H. J., van Rhenen D. J., Lansdorp P. M., van't Veer M. B., Langenhuijsen M. M., Engelfriet C. P., von dem Borne A. E. A comparison of surface marker analysis and FAB classification in acute myeloid leukemia. Blood. 1983 Mar;61(3):443–448. [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES