Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1997 Feb 1;99(3):526–533. doi: 10.1172/JCI119189

Neutrophil margination, sequestration, and emigration in the lungs of L-selectin-deficient mice.

N A Doyle 1, S D Bhagwan 1, B B Meek 1, G J Kutkoski 1, D A Steeber 1, T F Tedder 1, C M Doerschuk 1
PMCID: PMC507828  PMID: 9022088

Abstract

These studies tested the hypothesis that L-selectin plays a role in neutrophil traffic in the lungs, particularly in neutrophil margination, sequestration, and emigration, using L-selectin-deficient mice. No defect in neutrophil margination within either capillaries or arterioles and venules was observed in uninflamed lungs of L-selectin-deficient mice. The initial rapid sequestration of neutrophils within the pulmonary capillaries 1 min after intravascular injection of complement fragments was not prevented. In contrast, L-selectin did contribute to the prolonged neutrophil sequestration (> or = 5 min). Interestingly, neutrophil accumulation within noncapillary microvessels required L-selectin at both 1 and 5 min after complement injection. During bacterial pneumonias, L-selectin played a role in neutrophil accumulation within noncapillary microvessels in response to either Escherichia coli or Streptococcus pneumoniae and within capillaries in response to E. coli but not S. pneumoniae. However, L-selectin was not required for emigration of neutrophils or edema in response to either organism. These studies demonstrate a role for L-selectin in the prolonged sequestration of neutrophils in response to intravascular complement fragments, in the intracapillary accumulation of neutrophils during E. coli-induced pneumonia, and in the accumulation of neutrophils within noncapillary microvessels when induced by either intravascular complement fragments or

Full Text

The Full Text of this article is available as a PDF (216.1 KB).

Selected References

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

  1. Arbonés M. L., Ord D. C., Ley K., Ratech H., Maynard-Curry C., Otten G., Capon D. J., Tedder T. F. Lymphocyte homing and leukocyte rolling and migration are impaired in L-selectin-deficient mice. Immunity. 1994 Jul;1(4):247–260. doi: 10.1016/1074-7613(94)90076-0. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Carlos T. M., Harlan J. M. Leukocyte-endothelial adhesion molecules. Blood. 1994 Oct 1;84(7):2068–2101. [PubMed] [Google Scholar]
  4. Doerschuk C. M., Allard M. F., Hogg J. C. Neutrophil kinetics in rabbits during infusion of zymosan-activated plasma. J Appl Physiol (1985) 1989 Jul;67(1):88–95. doi: 10.1152/jappl.1989.67.1.88. [DOI] [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. The role of CD18-mediated adhesion in neutrophil sequestration induced by infusion of activated plasma in rabbits. Am J Respir Cell Mol Biol. 1992 Aug;7(2):140–148. doi: 10.1165/ajrcmb/7.2.140. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. 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]
  11. 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]
  12. 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]
  13. Hogg J. C. Neutrophil kinetics and lung injury. Physiol Rev. 1987 Oct;67(4):1249–1295. doi: 10.1152/physrev.1987.67.4.1249. [DOI] [PubMed] [Google Scholar]
  14. Inano H., English D., Doerschuk C. M. Effect of zymosan-activated plasma on the deformability of rabbit polymorphonuclear leukocytes. J Appl Physiol (1985) 1992 Oct;73(4):1370–1376. doi: 10.1152/jappl.1992.73.4.1370. [DOI] [PubMed] [Google Scholar]
  15. Jutila M. A., Berg E. L., Kishimoto T. K., Picker L. J., Bargatze R. F., Bishop D. K., Orosz C. G., Wu N. W., Butcher E. C. Inflammation-induced endothelial cell adhesion to lymphocytes, neutrophils, and monocytes. Role of homing receptors and other adhesion molecules. Transplantation. 1989 Nov;48(5):727–731. doi: 10.1097/00007890-198911000-00001. [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. Lewinsohn D. M., Bargatze R. F., Butcher E. C. Leukocyte-endothelial cell recognition: evidence of a common molecular mechanism shared by neutrophils, lymphocytes, and other leukocytes. J Immunol. 1987 Jun 15;138(12):4313–4321. [PubMed] [Google Scholar]
  18. Ley K., Bullard D. C., Arbonés M. L., Bosse R., Vestweber D., Tedder T. F., Beaudet A. L. Sequential contribution of L- and P-selectin to leukocyte rolling in vivo. J Exp Med. 1995 Feb 1;181(2):669–675. doi: 10.1084/jem.181.2.669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ley K., Tedder T. F. Leukocyte interactions with vascular endothelium. New insights into selectin-mediated attachment and rolling. J Immunol. 1995 Jul 15;155(2):525–528. [PubMed] [Google Scholar]
  20. Lien D. C., Wagner W. W., Jr, Capen R. L., Haslett C., Hanson W. L., Hofmeister S. E., Henson P. M., Worthen G. S. Physiological neutrophil sequestration in the lung: visual evidence for localization in capillaries. J Appl Physiol (1985) 1987 Mar;62(3):1236–1243. doi: 10.1152/jappl.1987.62.3.1236. [DOI] [PubMed] [Google Scholar]
  21. Ma X. L., Weyrich A. S., Lefer D. J., Buerke M., Albertine K. H., Kishimoto T. K., Lefer A. M. Monoclonal antibody to L-selectin attenuates neutrophil accumulation and protects ischemic reperfused cat myocardium. Circulation. 1993 Aug;88(2):649–658. doi: 10.1161/01.cir.88.2.649. [DOI] [PubMed] [Google Scholar]
  22. Motosugi H., Graham L., Noblitt T. W., Doyle N. A., Quinlan W. M., Li Y., Doerschuk C. M. Changes in neutrophil actin and shape during sequestration induced by complement fragments in rabbits. Am J Pathol. 1996 Sep;149(3):963–973. [PMC free article] [PubMed] [Google Scholar]
  23. Mulligan M. S., Miyasaka M., Tamatani T., Jones M. L., Ward P. A. Requirements for L-selectin in neutrophil-mediated lung injury in rats. J Immunol. 1994 Jan 15;152(2):832–840. [PubMed] [Google Scholar]
  24. Mulligan M. S., Polley M. J., Bayer R. J., Nunn M. F., Paulson J. C., Ward P. A. Neutrophil-dependent acute lung injury. Requirement for P-selectin (GMP-140). J Clin Invest. 1992 Oct;90(4):1600–1607. doi: 10.1172/JCI116029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Simon S. I., Burns A. R., Taylor A. D., Gopalan P. K., Lynam E. B., Sklar L. A., Smith C. W. L-selectin (CD62L) cross-linking signals neutrophil adhesive functions via the Mac-1 (CD11b/CD18) beta 2-integrin. J Immunol. 1995 Aug 1;155(3):1502–1514. [PubMed] [Google Scholar]
  27. Simon S. I., Rochon Y. P., Lynam E. B., Smith C. W., Anderson D. C., Sklar L. A. Beta 2-integrin and L-selectin are obligatory receptors in neutrophil aggregation. Blood. 1993 Aug 15;82(4):1097–1106. [PubMed] [Google Scholar]
  28. Steeber D. A., Green N. E., Sato S., Tedder T. F. Lyphocyte migration in L-selectin-deficient mice. Altered subset migration and aging of the immune system. J Immunol. 1996 Aug 1;157(3):1096–1106. [PubMed] [Google Scholar]
  29. Sweeney T. D., Leith D. E., Brain J. D. Restraining hamsters alters their breathing pattern. J Appl Physiol (1985) 1991 Mar;70(3):1271–1276. doi: 10.1152/jappl.1991.70.3.1271. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Tedder T. F., Steeber D. A., Pizcueta P. L-selectin-deficient mice have impaired leukocyte recruitment into inflammatory sites. J Exp Med. 1995 Jun 1;181(6):2259–2264. doi: 10.1084/jem.181.6.2259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Turunen J. P., Paavonen T., Majuri M. L., Tiisala S., Mattila P., Mennander A., Gahmberg C. G., Häyry P., Tamatani T., Miyasaka M. Sialyl Lewis(x)- and L-selectin-dependent site-specific lymphocyte extravasation into renal transplants during acute rejection. Eur J Immunol. 1994 May;24(5):1130–1136. doi: 10.1002/eji.1830240518. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. 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]
  35. Yang X. D., Karin N., Tisch R., Steinman L., McDevitt H. O. Inhibition of insulitis and prevention of diabetes in nonobese diabetic mice by blocking L-selectin and very late antigen 4 adhesion receptors. Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10494–10498. doi: 10.1073/pnas.90.22.10494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Yoder M. C., Checkley L. L., Giger U., Hanson W. L., Kirk K. R., Capen R. L., Wagner W. W., Jr Pulmonary microcirculatory kinetics of neutrophils deficient in leukocyte adhesion-promoting glycoproteins. J Appl Physiol (1985) 1990 Jul;69(1):207–213. doi: 10.1152/jappl.1990.69.1.207. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES