Skip to main content
Log in

Thromboxane-induced neutrophil adhesion to pulmonary microvascular and aortic endothelium is regulated by CD18

  • Original Articles
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Thromboxane (Tx) A2 generation and subsequent selective pulmonary sequestration of neutrophils (PMNs) is characteristic of several forms of the adult respiratory distress syndrome (ARDS). Therefore, we examined PMN-dependent adhesion to cultured pulmonary microvessel and aortic endothelium (EC) in response to U46,619 (Tx mimic). Nonstimulated PMNs were two fold more adherent to pulmonary microvessel HC than to aortic EC (P < 0.01). PMN pretreatment with Tx mimic (10−6 M) increased adhesion to both types of EC (P < 0.01). The Tx mimic-induced adhesion was blocked by receptor antagonists to Tx (SQ29,548) and to leukotrienes (FPL55,712), and by the anti-CD18 mAb TS1/18 (P < 0.01, all cases). Baseline PMN adhesion also was modulated by Tx, leukotrienes, and CD18, for both EC types. These results indicate pulmonary microvessel EC is intrinsically more adhesive for both nonstimulated and stimulated PMNs than aortic EC and that Tx mediates PMN-dependent adhesion by coupled interaction of Tx and LT receptors via CD 18 activation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Ratnoff, W.D., M.A. Matthay, M.Y.S. Wono, Y. Ito, K.J. Vu, J. Wiener-Kronish, andE.J. Goetzl. 1988. Sulfidopeptide-leukotriene peptidases in pulmonary edema fluid from patients with the adult respiratory distress syndrome.J. Clin. Immunol. 8:250–258.

    Google Scholar 

  2. Jackson, R.M., C.F. Veal, C.B. Alexander, A.L. Brannen, andJ.D. Fulmer. 1988. Reexpansion pulmonary edema: A potential role for free radicals in its pathogenesis.Am. Rev. Respir. Dis. 137:1165–1171.

    Google Scholar 

  3. Klausner, J.M., I.S. Paterson, L. Kobzik, C.R. Valeri, D. Shepro, andH.B. Hechtman. 1988. Lower torso ischemia induced lung injury is leukocyte dependent.Ann. Surg. 208:761–767.

    Google Scholar 

  4. Klausner, J.M., I.S. Paterson, L. Kobzik, C.R. Valeri, C. Shepro, andH.B. Hechtman. 1989. Oxygen free radicals mediate ischemia induced lung injury.Surgery 105:192–199.

    Google Scholar 

  5. Klausner, J.M., I.S. Paterson, G. Goldman, L. Kobzik, C.R. Valeri, D. Shepro, andH.B. Hechtman. 1989. Thromboxane A2 mediates increased pulmonary microvascular permeability following limb ischemia.Circ. Res. 64:1178–1189.

    Google Scholar 

  6. Utsunomiya, T., M.M. Krausz, B. Dunham, C.R. Valeri, L. Levine, D. Shepro, andH.B. Hechtman. 1982. Modification of inflammatory response to aspiration with ibuprofen.Am. J. Physiol. 243:H9D3-H910.

    Google Scholar 

  7. Sibbald, W.J., D. Campbell, R.R. Raper, F.S. Rutledge, andH. Cheung. 1989. The effects of prostaglandin E1 on lung injury complicating hyperdynamic sepsis in sheep.Am. Rev. Respir. Dis. 139:674–681.

    Google Scholar 

  8. Paterson, I.S., J.M. Klausner, G. Goldman, L. Kobzik, R. Welbourn, C.R. Valeri, D. Shepro, andH.B. Hechtman. 1989. Thromboxane mediates the ischemia-induced neutrophil oxidative burst.Surgery 106:224–229.

    Google Scholar 

  9. Klausner, J.M., L. Kobzik, C.R. Valeri, D. Shepro, andH.B. Hechtman. 1988. Selective lung leukosequestration after complement activation.J. Appl. Physiol. 65:80–88.

    Google Scholar 

  10. Perlman, M.B., A. Johmson, W. Jubiz, andA.B. Malik. 1989. Lipoxygenase products induce neutrophil activation and increase endothelial permeability after thrombin-induced pulmonary microembolism.Circ. Res. 64:62–73.

    Google Scholar 

  11. Shasby, D.M., S.S. Shasby, andM.J. Peach. 1985. Polymorphonuclear leukocyte. Arachidonate edema.J. Appl. Physiol. 59:47–55.

    Google Scholar 

  12. Harlan, J.M. 1985. Leukocyte endothelial interactions.Blood 65:513–525 (review).

    Google Scholar 

  13. Spagnuolo, P.H., J.J. Ellner, A. Hassid, andM.J. Dunn. 1980. Thromboxane A2 mediates augmented polymorphonuclear leukocyte adhesiveness.J. Clin. Invest. 66:406–414.

    Google Scholar 

  14. Vedder, N.B., R.K. Winn, C.L. Rice, E.Y. Chi, K.E. Arfors, andJ.M. Harlan. 1988. A monoclonal antibody to the adherence-promoting leukocyte glycoprotein, CD18, reduces organ injury and improves survival from hemorrhagic shock and resuscitation in rabbits.J. Clin. Invest. 81:939–944.

    Google Scholar 

  15. Vedder, N.B., B.W. Fouty, R.K. Winn, J.M. Harlan, andC.L. Rice. 1987. Role of neutrophils in generalized reperfusion injury associated with resuscitation from shock.Surgery 106:509–516.

    Google Scholar 

  16. Horgan, M.J., S.D. Wright, andA.B. Malik. 1989. Protective effect of monoclonal antibody IB4 directed against leukocyte adhesion glycoprotein CD18 in reperfusion lung injury.Am. Rev. Respir. Dis. 139:A303 (abstract).

    Google Scholar 

  17. Cooper, J.A., P.H. Neumann, S.D. Wright, andA.B. Malik. 1989. Pulmonary vascular sequestration of neutrophils in endotoxemia. Role of CD18 leukocyte surface glycoprotein.Am. Rev. Respir. Dis. 139:A301 (abstract).

    Google Scholar 

  18. Hynes, R.O. 1987. Integrins. A family of cell surface receptors.Cell 48:549–554 (review).

    Google Scholar 

  19. Tonnesen, M.G., D.C. Anderson, T.A. Springer, A. Knedler, N. Avdi, andP.M. Henson. 1989. Adherence of neutrophils to cultured human microvascular endothelial cells. Stimulation by chemotactic peptides and lipid mediators and dependence upon the Mac-1, LFA-1, p150,95 glycoprotein family.J. Clin. Invest. 83:637–646.

    Google Scholar 

  20. Harlan, J.M., P.D. Killen, F.M. Senecal, B.R. Schwartz, E.K. Yee, R.F. Taylor, P.G. Beatty, T.H. Price, andH.D. Ochs. 1985. The role of neutrophil membrane glycoprotein GP-150 in neutrophil adherence to endothelium in vitro.Blood 66:167–178.

    Google Scholar 

  21. Schleiffenbaum, B., R. Moser, M. Patarroyo, andJ. Fehr. 1989. The cell surface glycoprotein Mac-1 (CD11b/CD18) mediates neutrophil adhesion and modulates degranulation independently of its quantitative cell surface expression.J. Immunol. 142:3537–3545.

    Google Scholar 

  22. Arnaout, M.-A., L.L. Lanier, andD.V. Faller. 1988. Relative contribution of the leukocyte molecules Mol, LFA-1, and p150,95 (LeuM5) in adhesion of granulocytes and monocytes to vascular endothelium is tissueand stimulus-specific.J. Cell. Physiol. 137:305–307.

    Google Scholar 

  23. Sanchez-Madrid, F.J., A. Nagy, E. Robbins, P. Simon, andT.A. Springer. 1983. A human leukocyte differentiation antigen family with distinct alpha subunits and a common beta subunit. The lymphocyte function-associated antigen (LFA-1), the C3bi complement receptor (OKM1/Mac-1) and the pl50,95 molecule.J. Exp. Med. 158:1785–1803.

    Google Scholar 

  24. Pohlman, T.H., K.A. Stanness, P.G. Beatty, H.D. Ochs, andJ.M. Harlan. 1986. An endothelial cell surface factor(s) induced in vitro by lipopolysaccharide, interleukin 1, and tumor necrosis factor-a increases neutrophil adherence by a CD18-dependent mechanism.J. Immunol. 136:4548–4555.

    Google Scholar 

  25. Dustin, M.L., R. Rothlein, A.K. Bhan, C.A. Dinarelo, andT.A. Springer. 1986. Induction by IL 1 and interferon-y. Tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1).J. Immunol. 137:245–254.

    Google Scholar 

  26. Staunton, D.E., S.D. Marlin, C. Stratowa, M.L. Dustin, andT.A. Springer. 1988. Primary structure of ICAM-1 demonstrates interaction between members of the immunoglobulin and integrin supergene families.Cell 52:925–933.

    Google Scholar 

  27. Barton, R.W., R. Rothlein, J. Ksiazek, andC. Kennedy. 1989. The effect of anti-intercellular adhesion molecule-1 on phorbol-ester-induced rabbit lung inflammation.J. Immunol 143:1278–1282.

    Google Scholar 

  28. Zimmerman, G.A., andT.M. McIntyre. 1988. Neutrophil adherence to human endothelium in vitro occurs by CD18 (Mol,Mac-1/LFA-1/GP150,95) glycoprotein-dependent and -independent mechanisms.J. Clin. Invest. 81:531–537.

    Google Scholar 

  29. Slotman, G.J., C. Teplitz, S.A. Yellin, andR. Farruyir. 1987. Interaction of thromboxane A2 and tissue pathology during graded bacteremia.J. Trauma 27:167–175.

    Google Scholar 

  30. Chung-Welch, N., D. Shepro, B. Dunham, andH.B. Hechtman. 1988. Prostacyclin and prostaglandin E2 secretions by bovine pulmonary microvessel endothelial cells are altered by changes in culture conditions.J. Cell. Physiol. 135:224–234.

    Google Scholar 

  31. Shepro, D., M. Rosenthal, J. Batbouta, L.S. Roblee, andF.A. Belamarich. 1974. The cultivation of aortic endothelium.Anat. Rec. 78:523.

    Google Scholar 

  32. Doukas, J., D. Shepro, andH.B. Hechtman. 1987. Vasoactive amines directly modify endothelial cells to affect polymorphonuclear leukocyte diapedesis in vitro.Blood 69:1563–1569.

    Google Scholar 

  33. Chung-Welch, N., W.F. Patton, G.P.A. Yen-Patton, H.B. Hechtman, andD. Shepro. 1989. Phenotypic comparison between mesothelial and microvascular endothelial cell lineages using conventional endothelial cell markers, cytoskeletal protein markers and in vitro assays of angiogenic potential.Differentiation 42:44–53.

    Google Scholar 

  34. Patton, W.F., M.U. Yoon, J.S. Alexander, N. Chung-Welch, H.B. Hechtman, andD. Shepro. 1990. Expression of simple epithelial cytokeratins in bovine pulmonary microvascular endothelial cells.J. Cell. Physiol. 143:140–144.

    Google Scholar 

  35. English, D., andB.R. Anderson. 1974. Single-step separation of red blood cells, granulocytes and mononuclear leukocytes on discontinuous density gradients of Ficoll-Hypaque.J. Immunol. Methods 5:249

    Google Scholar 

  36. Doukas, J., H.B. Hechtman, andD. Shepro. 1989. Vasoactive amines and eicosanoids interactively regulate both polymorphonuclear leukocyte diapedesis and albumin permeability in vitro.Microvasc. Res. 37:125–137.

    Google Scholar 

  37. Doukas, J., H.B. Hechtman, andD. Shepro. 1988. Endothelial-secreted arachidonic acid metabolites modulate polymorphonuclear leukocyte chemotaxis and diapedesis in vitro.Blood 71:771–779.

    Google Scholar 

  38. Zimmerman, G.A., G.A. Wiseman, andH.R. Hill. 1985. Human endothelial cells modulate granulocyte adherence and chemotaxis.J. Immunol. 134:1866–1874.

    Google Scholar 

  39. Smith, C.W., S.D. Marlin, R. Rothlein, C. Toman, andD.C. Anderson. 1989. Cooperative interactions of LFA-1 and MAC-1 with intercellular adhesion molecule-1 in facilitating adherence and transendcthelial migration of human neutrophils in vitro.J. Clin. Invest. 83:2008–2017.

    Google Scholar 

  40. Bevilacqua, M.P., J.S. Pober, M.E. Wheeler, R.S. Cotran, andM.A. Gimbrone, Jr. 1985. Interleukin 1 acts on cultured human vascular endothelium to increase the adhesion of polymorphonuclear leukocytes, monocytes and related cell lines.J. Clin. Invest. 76:2003–2011.

    Google Scholar 

  41. Tonneson, M.G., L.A. Smedley, andP.M. Henson. 1984. Neutrophil-endothelial cell interactions. Modulation of neutrophil adhesiveness induced by complement fragments C5a and C5adesArg and formyl-methionyl-leucyl-phenylalanine in vitro.J. Clin. Invest. 74:1581–1592.

    Google Scholar 

  42. Zar, J.H. 1974. Biostatiiitical Analysis. Prentice-Hall, Englewood Cliffs, New Jersey.

    Google Scholar 

  43. Miller, L.J., D.F. Baimton, N. Borregard, andT.A. Springer. 1987. Stimulated mobilization of monocyte Mac-1 and p150,95 adhesion proteins from an intracellular vesicular compartment to the cell surface.J. Clin. Invest. 80:535–544.

    Google Scholar 

  44. Grimminger, F., M. Menger, G. Becker, andW. Seeger. 1989. Potentiation of leukotriene production following sequestration of neutrophils in isolated lungs. Indirect evidence for intercellular leukotriene A4 transfer.Blood 72:1687–1692.

    Google Scholar 

  45. Gimbrone, M.A., Jr., A.F. Brock, andA.I. Schafer. 1984. Leukotriene B4 stimulates polymorphonuclear leukocyte: adhesion to cultured vascular endothelial cells.J. Clin. Invest. 74:1552–1555.

    Google Scholar 

  46. Simpson, P.J., R.F. Todd, J.C. Fantone, J.K. Mickelson, J.D. Griffen, andB.R. Lucchesi. 1988. Reduction of experimental canine myocardial reperfusion injury by a monoclonal antibody (anti-Mo1 anti-CD11b) that inhibits leukocyte adhesion.J. Clin. Invest. 81:624.

    Google Scholar 

  47. Kaslovsky, R.A., M.J. Horgan, J. Everitt, S.D. Wright, andA.B. Malik. 1989. Leukocyte CD18 adhesive glycoprotein is involved in neutrophil-dependent pulmonary edema induced by opsonized zymosan.Am. Rev. Respir. Dis. 139:A303 (abstract).

    Google Scholar 

  48. Winn, R., J. Harlan, B. Nadir, L. Harker, andJ. Hildebrandt. 1983. Thromboxane A2 mediates lung vasoconstriction but not permeability after endotoxin.J. Clin. Invest. 72:911–918.

    Google Scholar 

  49. Doerschuk, C.M., R.K. Winn, H.O. Coxson, andJ.M. Harlan. 1990. CD18-dependent and-independent mechanisms of neutrophil emigration in the pulmonary and systemic microcirculation of rabbits.J. Immunol. 144:2327–2333.

    Google Scholar 

  50. Toothill, V.J., J.A. Van Mourik, H.K. Niewenhuis, M.J. Metzelaar, andJ.D. Pearson. 1990. Characterization of the enhanced adhesion of neutrophil leukocytes to thrombin-stimulated endothelial cells.J. Immunol. 145:283–291.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This research was supported in part by: USPHS, NHLBI 16714, 43875, 33104, and GM24891.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wiles, M.E., Welbourn, R., Goldman, G. et al. Thromboxane-induced neutrophil adhesion to pulmonary microvascular and aortic endothelium is regulated by CD18. Inflammation 15, 181–199 (1991). https://doi.org/10.1007/BF00918645

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00918645

Keywords

Navigation