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. 1992 Nov;90(5):1687–1696. doi: 10.1172/JCI116041

Recruitment of CD11b/CD18 to the neutrophil surface and adherence-dependent cell locomotion.

B J Hughes 1, J C Hollers 1, E Crockett-Torabi 1, C W Smith 1
PMCID: PMC443225  PMID: 1358917

Abstract

Chemotactic stimulation of neutrophils results in translocation of CD11b/CD18 (Mac-1) from intracellular storage pools to the cell surface. Though results from several laboratories indicate that the newly arrived surface Mac-1 is not involved in the adherence induced by the initial stimulus, the present study addresses the hypothesis that this Mac-1 plays a role in subsequent adherence-dependent functions. The response of human neutrophils to changing concentrations of a chemotactic stimulus was evaluated by determining the amount of newly arrived surface Mac-1, and Mac-1-dependent adhesion and locomotion. Small step-wise increases in the concentration of f-Met-Leu-Phe (FMLP) resulted in proportional stepwise increases in surface Mac-1 that plateaued within 2-4 min. This newly arrived Mac-1 supported adhesion to protein-coated surfaces only when the cells were exposed to an additional increase in the FMLP stimulus level. Adherence-dependent cellular locomotion was evaluated in chambers that allowed rapid changes in the stimulus concentration. Repeated small increments in the stimulus level at 200-s intervals resulted in significantly longer migration paths than a single-step increase in the stimulus. The results support the hypothesis that small increments in the chemotactic stimulus bring Mac-1 to the cell surface, and this newly mobilized Mac-1 is available for adherence-dependent locomotion with subsequent increases in the concentration of the stimulus.

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Selected References

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  1. Anderson D. C., Hughes B. J., Smith C. W. Abnormal mobility of neonatal polymorphonuclear leukocytes. Relationship to impaired redistribution of surface adhesion sites by chemotactic factor or colchicine. J Clin Invest. 1981 Oct;68(4):863–874. doi: 10.1172/JCI110341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anderson D. C., Miller L. J., Schmalstieg F. C., Rothlein R., Springer T. A. Contributions of the Mac-1 glycoprotein family to adherence-dependent granulocyte functions: structure-function assessments employing subunit-specific monoclonal antibodies. J Immunol. 1986 Jul 1;137(1):15–27. [PubMed] [Google Scholar]
  3. Anderson D. C., Rothlein R., Marlin S. D., Krater S. S., Smith C. W. Impaired transendothelial migration by neonatal neutrophils: abnormalities of Mac-1 (CD11b/CD18)-dependent adherence reactions. Blood. 1990 Dec 15;76(12):2613–2621. [PubMed] [Google Scholar]
  4. Bainton D. F., Miller L. J., Kishimoto T. K., Springer T. A. Leukocyte adhesion receptors are stored in peroxidase-negative granules of human neutrophils. J Exp Med. 1987 Dec 1;166(6):1641–1653. doi: 10.1084/jem.166.6.1641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Berger M., O'Shea J., Cross A. S., Folks T. M., Chused T. M., Brown E. J., Frank M. M. Human neutrophils increase expression of C3bi as well as C3b receptors upon activation. J Clin Invest. 1984 Nov;74(5):1566–1571. doi: 10.1172/JCI111572. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Boxer L. A., Coates T. D., Haak R. A., Wolach J. B., Hoffstein S., Baehner R. L. Lactoferrin deficiency associated with altered granulocyte function. N Engl J Med. 1982 Aug 12;307(7):404–410. doi: 10.1056/NEJM198208123070704. [DOI] [PubMed] [Google Scholar]
  7. Boxer L. A., Haak R. A., Yang H. H., Wolach J. B., Whitcomb J. A., Butterick C. J., Baehner R. L. Membrane-bound lactoferrin alters the surface properties of polymorphonuclear leukocytes. J Clin Invest. 1982 Nov;70(5):1049–1057. doi: 10.1172/JCI110692. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Buyon J. P., Abramson S. B., Philips M. R., Slade S. G., Ross G. D., Weissmann G., Winchester R. J. Dissociation between increased surface expression of gp165/95 and homotypic neutrophil aggregation. J Immunol. 1988 May 1;140(9):3156–3160. [PubMed] [Google Scholar]
  9. Buyon J. P., Slade S. G., Reibman J., Abramson S. B., Philips M. R., Weissmann G., Winchester R. Constitutive and induced phosphorylation of the alpha- and beta-chains of the CD11/CD18 leukocyte integrin family. Relationship to adhesion-dependent functions. J Immunol. 1990 Jan 1;144(1):191–197. [PubMed] [Google Scholar]
  10. Detmers P. A., Wright S. D., Olsen E., Kimball B., Cohn Z. A. Aggregation of complement receptors on human neutrophils in the absence of ligand. J Cell Biol. 1987 Sep;105(3):1137–1145. doi: 10.1083/jcb.105.3.1137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dransfield I., Hogg N. Regulated expression of Mg2+ binding epitope on leukocyte integrin alpha subunits. EMBO J. 1989 Dec 1;8(12):3759–3765. doi: 10.1002/j.1460-2075.1989.tb08552.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Francis J. W., Todd R. F., 3rd, Boxer L. A., Petty H. R. Sequential expression of cell surface C3bi receptors during neutrophil locomotion. J Cell Physiol. 1989 Sep;140(3):519–523. doi: 10.1002/jcp.1041400317. [DOI] [PubMed] [Google Scholar]
  14. Furie M. B., Tancinco M. C., Smith C. W. Monoclonal antibodies to leukocyte integrins CD11a/CD18 and CD11b/CD18 or intercellular adhesion molecule-1 inhibit chemoattractant-stimulated neutrophil transendothelial migration in vitro. Blood. 1991 Oct 15;78(8):2089–2097. [PubMed] [Google Scholar]
  15. Gallin J. I., Fletcher M. P., Seligmann B. E., Hoffstein S., Cehrs K., Mounessa N. Human neutrophil-specific granule deficiency: a model to assess the role of neutrophil-specific granules in the evolution of the inflammatory response. Blood. 1982 Jun;59(6):1317–1329. [PubMed] [Google Scholar]
  16. Jaconi M. E., Theler J. M., Schlegel W., Appel R. D., Wright S. D., Lew P. D. Multiple elevations of cytosolic-free Ca2+ in human neutrophils: initiation by adherence receptors of the integrin family. J Cell Biol. 1991 Mar;112(6):1249–1257. doi: 10.1083/jcb.112.6.1249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Marks P. W., Hendey B., Maxfield F. R. Attachment to fibronectin or vitronectin makes human neutrophil migration sensitive to alterations in cytosolic free calcium concentration. J Cell Biol. 1991 Jan;112(1):149–158. doi: 10.1083/jcb.112.1.149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Marks P. W., Maxfield F. R. Transient increases in cytosolic free calcium appear to be required for the migration of adherent human neutrophils. J Cell Biol. 1990 Jan;110(1):43–52. doi: 10.1083/jcb.110.1.43. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Miller L. J., Bainton D. F., Borregaard N., Springer T. A. Stimulated mobilization of monocyte Mac-1 and p150,95 adhesion proteins from an intracellular vesicular compartment to the cell surface. J Clin Invest. 1987 Aug;80(2):535–544. doi: 10.1172/JCI113102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. O'Shea J. J., Brown E. J., Seligmann B. E., Metcalf J. A., Frank M. M., Gallin J. I. Evidence for distinct intracellular pools of receptors for C3b and C3bi in human neutrophils. J Immunol. 1985 Apr;134(4):2580–2587. [PubMed] [Google Scholar]
  22. Oppenheimer-Marks N., Davis L. S., Bogue D. T., Ramberg J., Lipsky P. E. Differential utilization of ICAM-1 and VCAM-1 during the adhesion and transendothelial migration of human T lymphocytes. J Immunol. 1991 Nov 1;147(9):2913–2921. [PubMed] [Google Scholar]
  23. Oseas R., Yang H. H., Baehner R. L., Boxer L. A. Lactoferrin: a promoter of polymorphonuclear leukocyte adhesiveness. Blood. 1981 May;57(5):939–945. [PubMed] [Google Scholar]
  24. Petrequin P. R., Todd R. F., 3rd, Smolen J. E., Boxer L. A. Expression of specific granule markers on the cell surface of neutrophil cytoplasts. Blood. 1986 Apr;67(4):1119–1125. [PubMed] [Google Scholar]
  25. Petty H. R., Francis J. W., Todd R. F., 3rd, Petrequin P., Boxer L. A. Neutrophil C3bi receptors: formation of membrane clusters during cell triggering requires intracellular granules. J Cell Physiol. 1987 Nov;133(2):235-42, 256. doi: 10.1002/jcp.1041330206. [DOI] [PubMed] [Google Scholar]
  26. Philips M. R., Buyon J. P., Winchester R., Weissmann G., Abramson S. B. Up-regulation of the iC3b receptor (CR3) is neither necessary nor sufficient to promote neutrophil aggregation. J Clin Invest. 1988 Aug;82(2):495–501. doi: 10.1172/JCI113623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rosen H., Gordon S. Monoclonal antibody to the murine type 3 complement receptor inhibits adhesion of myelomonocytic cells in vitro and inflammatory cell recruitment in vivo. J Exp Med. 1987 Dec 1;166(6):1685–1701. doi: 10.1084/jem.166.6.1685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rosen H. Role of CR3 in induced myelomonocytic recruitment: insights from in vivo monoclonal antibody studies in the mouse. J Leukoc Biol. 1990 Nov;48(5):465–469. doi: 10.1002/jlb.48.5.465. [DOI] [PubMed] [Google Scholar]
  29. Schmalstieg F. C., Rudloff H. E., Hillman G. R., Anderson D. C. Two-dimensional and three-dimensional movement of human polymorphonuclear leukocytes: two fundamentally different mechanisms of locomotion [corrected]. J Leukoc Biol. 1986 Dec;40(6):677–691. doi: 10.1002/jlb.40.6.677. [DOI] [PubMed] [Google Scholar]
  30. Shappell S. B., Toman C., Anderson D. C., Taylor A. A., Entman M. L., Smith C. W. Mac-1 (CD11b/CD18) mediates adherence-dependent hydrogen peroxide production by human and canine neutrophils. J Immunol. 1990 Apr 1;144(7):2702–2711. [PubMed] [Google Scholar]
  31. Smith C. W., Hollers J. C. Motility and adhesiveness in human neutrophils. Redistribution of chemotactic factor-induced adhesion sites. J Clin Invest. 1980 Apr;65(4):804–812. doi: 10.1172/JCI109731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Smith C. W., Hollers J. C., Patrick R. A., Hassett C. Motility and adhesiveness in human neutrophils. Effects of chemotactic factors. J Clin Invest. 1979 Feb;63(2):221–229. doi: 10.1172/JCI109293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. 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]
  34. Smith C. W., Marlin S. D., Rothlein R., Toman C., Anderson D. C. Cooperative interactions of LFA-1 and Mac-1 with intercellular adhesion molecule-1 in facilitating adherence and transendothelial migration of human neutrophils in vitro. J Clin Invest. 1989 Jun;83(6):2008–2017. doi: 10.1172/JCI114111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. 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]
  36. Todd R. F., 3rd, Arnaout M. A., Rosin R. E., Crowley C. A., Peters W. A., Babior B. M. Subcellular localization of the large subunit of Mo1 (Mo1 alpha; formerly gp 110), a surface glycoprotein associated with neutrophil adhesion. J Clin Invest. 1984 Oct;74(4):1280–1290. doi: 10.1172/JCI111538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Tranquillo R. T., Lauffenburger D. A., Zigmond S. H. A stochastic model for leukocyte random motility and chemotaxis based on receptor binding fluctuations. J Cell Biol. 1988 Feb;106(2):303–309. doi: 10.1083/jcb.106.2.303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Van Epps D. E., Potter J., Vachula M., Smith C. W., Anderson D. C. Suppression of human lymphocyte chemotaxis and transendothelial migration by anti-LFA-1 antibody. J Immunol. 1989 Nov 15;143(10):3207–3210. [PubMed] [Google Scholar]
  39. Vedder N. B., Harlan J. M. Increased surface expression of CD11b/CD18 (Mac-1) is not required for stimulated neutrophil adherence to cultured endothelium. J Clin Invest. 1988 Mar;81(3):676–682. doi: 10.1172/JCI113372. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Wright S. D., Jong M. T. Adhesion-promoting receptors on human macrophages recognize Escherichia coli by binding to lipopolysaccharide. J Exp Med. 1986 Dec 1;164(6):1876–1888. doi: 10.1084/jem.164.6.1876. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Wright S. D., Levin S. M., Jong M. T., Chad Z., Kabbash L. G. CR3 (CD11b/CD18) expresses one binding site for Arg-Gly-Asp-containing peptides and a second site for bacterial lipopolysaccharide. J Exp Med. 1989 Jan 1;169(1):175–183. doi: 10.1084/jem.169.1.175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Zigmond S. H. Ability of polymorphonuclear leukocytes to orient in gradients of chemotactic factors. J Cell Biol. 1977 Nov;75(2 Pt 1):606–616. doi: 10.1083/jcb.75.2.606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Zigmond S. H. Chemotaxis by polymorphonuclear leukocytes. J Cell Biol. 1978 May;77(2):269–287. doi: 10.1083/jcb.77.2.269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Zigmond S. H., Slonczewski J. L., Wilde M. W., Carson M. Polymorphonuclear leukocyte locomotion is insensitive to lowered cytoplasmic calcium levels. Cell Motil Cytoskeleton. 1988;9(2):184–189. doi: 10.1002/cm.970090210. [DOI] [PubMed] [Google Scholar]
  45. Zigmond S. H., Sullivan S. J. Sensory adaptation of leukocytes to chemotactic peptides. J Cell Biol. 1979 Aug;82(2):517–527. doi: 10.1083/jcb.82.2.517. [DOI] [PMC free article] [PubMed] [Google Scholar]

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