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The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1996 Aug 1;184(2):639–645. doi: 10.1084/jem.184.2.639

Selectins and neutrophil traffic: margination and Streptococcus pneumoniae-induced emigration in murine lungs

PMCID: PMC2192708  PMID: 8760817

Abstract

The roles of selectins in the pulmonary margination and emigration of neutrophils were investigated by using mice genetically deficient in both E- and P-selectins (E/P mutants) and/or by intravenous injections of fucoidin (inhibiting both L- and P-selectins). E/P mutants were neutrophilic (14.7 +/- 4.9 x 10(6) vs. 0.8 +/- 0.1 x 10(6) neutrophils/ml). This neutrophilia was associated with increased margination of neutrophils within pulmonary capillaries (39.7 +/- 9.4 vs. 4.6 +/- 1.1 neutrophil profiles per 100 red blood cell profiles) but no change in margination within noncapillary pulmonary microvessels. After intratracheal instillation of Streptococcus pneumoniae, lungs of E/P mutants displayed increased neutrophil emigration (564 +/- 92 vs. 116 +/- 19 neutrophils per 100 alveolar profiles), edema (5.3 +/- 1.5 vs. 1.5 +/- 0.4 microliter/g body weight), and histologic evidence of lung injury compared with those in wild-type (WT). Fucoidin treatment did not affect neutrophil emigration during streptococcal pneumonia in WT or E/P mice. During pneumonia, the number of white blood cells (WBC) tethered to or spread upon the noncapillary vessel endothelium increased in both WT and E/P lungs. These are the first data demonstrating that neutrophil margination in uninfected pulmonary capillaries does not require E- and P-selectins; that streptococcal pneumonia induces an E- and P-selectin-independent increase in WBC interactions with noncapillary endothelium; and that migration of neutrophils to alveoli can occur despite deficiency or inhibition of all of the known selectins.

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Selected References

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  1. Brown D. M., Drost E., Donaldson K., MacNee W. Deformability and CD11/CD18 expression of sequestered neutrophils in normal and inflamed lungs. Am J Respir Cell Mol Biol. 1995 Nov;13(5):531–539. doi: 10.1165/ajrcmb.13.5.7576688. [DOI] [PubMed] [Google Scholar]
  2. Bullard D. C., Kunkel E. J., Kubo H., Hicks M. J., Lorenzo I., Doyle N. A., Doerschuk C. M., Ley K., Beaudet A. L. Infectious susceptibility and severe deficiency of leukocyte rolling and recruitment in E-selectin and P-selectin double mutant mice. J Exp Med. 1996 May 1;183(5):2329–2336. doi: 10.1084/jem.183.5.2329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bullard D. C., Qin L., Lorenzo I., Quinlin W. M., Doyle N. A., Bosse R., Vestweber D., Doerschuk C. M., Beaudet A. L. P-selectin/ICAM-1 double mutant mice: acute emigration of neutrophils into the peritoneum is completely absent but is normal into pulmonary alveoli. J Clin Invest. 1995 Apr;95(4):1782–1788. doi: 10.1172/JCI117856. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Carlos T. M., Harlan J. M. Leukocyte-endothelial adhesion molecules. Blood. 1994 Oct 1;84(7):2068–2101. [PubMed] [Google Scholar]
  5. Doerschuk C. M., Beyers N., Coxson H. O., Wiggs B., Hogg J. C. Comparison of neutrophil and capillary diameters and their relation to neutrophil sequestration in the lung. J Appl Physiol (1985) 1993 Jun;74(6):3040–3045. doi: 10.1152/jappl.1993.74.6.3040. [DOI] [PubMed] [Google Scholar]
  6. Doerschuk C. M., Markos J., Coxson H. O., English D., Hogg J. C. Quantitation of neutrophil migration in acute bacterial pneumonia in rabbits. J Appl Physiol (1985) 1994 Dec;77(6):2593–2599. doi: 10.1152/jappl.1994.77.6.2593. [DOI] [PubMed] [Google Scholar]
  7. Doerschuk C. M., Winn R. K., Coxson H. O., Harlan J. M. CD18-dependent and -independent mechanisms of neutrophil emigration in the pulmonary and systemic microcirculation of rabbits. J Immunol. 1990 Mar 15;144(6):2327–2333. [PubMed] [Google Scholar]
  8. Downey G. P., Worthen G. S., Henson P. M., Hyde D. M. Neutrophil sequestration and migration in localized pulmonary inflammation. Capillary localization and migration across the interalveolar septum. Am Rev Respir Dis. 1993 Jan;147(1):168–176. doi: 10.1164/ajrccm/147.1.168. [DOI] [PubMed] [Google Scholar]
  9. Frenette P. S., Mayadas T. N., Rayburn H., Hynes R. O., Wagner D. D. Susceptibility to infection and altered hematopoiesis in mice deficient in both P- and E-selectins. Cell. 1996 Feb 23;84(4):563–574. doi: 10.1016/s0092-8674(00)81032-6. [DOI] [PubMed] [Google Scholar]
  10. Gaboury J. P., Kubes P. Reductions in physiologic shear rates lead to CD11/CD18-dependent, selectin-independent leukocyte rolling in vivo. Blood. 1994 Jan 15;83(2):345–350. [PubMed] [Google Scholar]
  11. Gebb S. A., Graham J. A., Hanger C. C., Godbey P. S., Capen R. L., Doerschuk C. M., Wagner W. W., Jr Sites of leukocyte sequestration in the pulmonary microcirculation. J Appl Physiol (1985) 1995 Aug;79(2):493–497. doi: 10.1152/jappl.1995.79.2.493. [DOI] [PubMed] [Google Scholar]
  12. Hellewell P. G., Young S. K., Henson P. M., Worthen G. S. Disparate role of the beta 2-integrin CD18 in the local accumulation of neutrophils in pulmonary and cutaneous inflammation in the rabbit. Am J Respir Cell Mol Biol. 1994 Apr;10(4):391–398. doi: 10.1165/ajrcmb.10.4.7510985. [DOI] [PubMed] [Google Scholar]
  13. Hensley P., McDevitt P. J., Brooks I., Trill J. J., Feild J. A., McNulty D. E., Connor J. R., Griswold D. E., Kumar N. V., Kopple K. D. The soluble form of E-selectin is an asymmetric monomer. Expression, purification, and characterization of the recombinant protein. J Biol Chem. 1994 Sep 30;269(39):23949–23958. [PubMed] [Google Scholar]
  14. Hogg J. C., Doerschuk C. M. Leukocyte traffic in the lung. Annu Rev Physiol. 1995;57:97–114. doi: 10.1146/annurev.ph.57.030195.000525. [DOI] [PubMed] [Google Scholar]
  15. Kuebler W. M., Kuhnle G. E., Groh J., Goetz A. E. Leukocyte kinetics in pulmonary microcirculation: intravital fluorescence microscopic study. J Appl Physiol (1985) 1994 Jan;76(1):65–71. doi: 10.1152/jappl.1994.76.1.65. [DOI] [PubMed] [Google Scholar]
  16. Kumasaka T., Quinlan W. M., Doyle N. A., Condon T. P., Sligh J., Takei F., Beaudet A. l., Bennett C. F., Doerschuk C. M. Role of the intercellular adhesion molecule-1(ICAM-1) in endotoxin-induced pneumonia evaluated using ICAM-1 antisense oligonucleotides, anti-ICAM-1 monoclonal antibodies, and ICAM-1 mutant mice. J Clin Invest. 1996 May 15;97(10):2362–2369. doi: 10.1172/JCI118679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ley K., Linnemann G., Meinen M., Stoolman L. M., Gaehtgens P. Fucoidin, but not yeast polyphosphomannan PPME, inhibits leukocyte rolling in venules of the rat mesentery. Blood. 1993 Jan 1;81(1):177–185. [PubMed] [Google Scholar]
  18. McEver R. P., Moore K. L., Cummings R. D. Leukocyte trafficking mediated by selectin-carbohydrate interactions. J Biol Chem. 1995 May 12;270(19):11025–11028. doi: 10.1074/jbc.270.19.11025. [DOI] [PubMed] [Google Scholar]
  19. Mulligan M. S., Lowe J. B., Larsen R. D., Paulson J., Zheng Z. L., DeFrees S., Maemura K., Fukuda M., Ward P. A. Protective effects of sialylated oligosaccharides in immune complex-induced acute lung injury. J Exp Med. 1993 Aug 1;178(2):623–631. doi: 10.1084/jem.178.2.623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mulligan M. S., Vaporciyan A. A., Warner R. L., Jones M. L., Foreman K. E., Miyasaka M., Todd R. F., 3rd, Ward P. A. Compartmentalized roles for leukocytic adhesion molecules in lung inflammatory injury. J Immunol. 1995 Feb 1;154(3):1350–1363. [PubMed] [Google Scholar]
  21. Mulligan M. S., Varani J., Dame M. K., Lane C. L., Smith C. W., Anderson D. C., Ward P. A. Role of endothelial-leukocyte adhesion molecule 1 (ELAM-1) in neutrophil-mediated lung injury in rats. J Clin Invest. 1991 Oct;88(4):1396–1406. doi: 10.1172/JCI115446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mulligan M. S., Watson S. R., Fennie C., Ward P. A. Protective effects of selectin chimeras in neutrophil-mediated lung injury. J Immunol. 1993 Dec 1;151(11):6410–6417. [PubMed] [Google Scholar]
  23. Shimaoka M., Ikeda M., Iida T., Taenaka N., Yoshiya I., Honda T. Fucoidin, a potent inhibitor of leukocyte rolling, prevents neutrophil influx into phorbol-ester-induced inflammatory sites in rabbit lungs. Am J Respir Crit Care Med. 1996 Jan;153(1):307–311. doi: 10.1164/ajrccm.153.1.8542135. [DOI] [PubMed] [Google Scholar]
  24. Tedder T. F., Steeber D. A., Chen A., Engel P. The selectins: vascular adhesion molecules. FASEB J. 1995 Jul;9(10):866–873. [PubMed] [Google Scholar]
  25. Ulich T. R., Howard S. C., Remick D. G., Yi E. S., Collins T., Guo K., Yin S., Keene J. L., Schmuke J. J., Steininger C. N. Intratracheal administration of endotoxin and cytokines: VIII. LPS induces E-selectin expression; anti-E-selectin and soluble E-selectin inhibit acute inflammation. Inflammation. 1994 Aug;18(4):389–398. doi: 10.1007/BF01534436. [DOI] [PubMed] [Google Scholar]
  26. Wiggs B. R., English D., Quinlan W. M., Doyle N. A., Hogg J. C., Doerschuk C. M. Contributions of capillary pathway size and neutrophil deformability to neutrophil transit through rabbit lungs. J Appl Physiol (1985) 1994 Jul;77(1):463–470. doi: 10.1152/jappl.1994.77.1.463. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Worthen G. S., Schwab B., 3rd, Elson E. L., Downey G. P. Mechanics of stimulated neutrophils: cell stiffening induces retention in capillaries. Science. 1989 Jul 14;245(4914):183–186. doi: 10.1126/science.2749255. [DOI] [PubMed] [Google Scholar]

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