Abstract
L-selectin, a cell surface adhesion molecule that is expressed by most leukocytes, mediates leukocyte rolling along vascular endothelium at sites of inflammation. The contribution of L-selectin to leukocyte migration in models of chronic inflammation was assessed by using mice that lack cell surface L-selectin expression. Significant inhibition of neutrophil (56-62%), lymphocyte (70-75%), and monocyte (72-78%) migration into an inflamed peritoneum was observed 24 and 48 h after administration of thioglycollate, an inflammatory stimulus. L-selectin- deficient mice were also significantly impaired in delayed-type hypersensitivity reactions. Footpad swelling in response to sheep red blood cell challenge was reduced 75% in L-selectin-deficient mice compared with wild-type mice. Ear swelling in a model of contact hypersensitivity induced by oxazolone challenge was also reduced by 69% compared to wild-type mice. Consistent with L-selectin-mediating leukocyte migration into diverse vascular beds during inflammation, L- selectin-deficient mice were significantly resistant to death resulting from lipopolysaccharide (LPS)-induced toxic shock. LPS administration resulted in a 90% mortality rate in control mice after 24 h, while there was a 90% survival rate in L-selectin-deficient mice. These results demonstrate that L-selectin plays a prominent role in leukocyte homing to nonlymphoid tissues during inflammation and that blocking this process can be beneficial during pathological inflammatory responses.
Full Text
The Full Text of this article is available as a PDF (554.9 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- 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]
- Brady H. R., Spertini O., Jimenez W., Brenner B. M., Marsden P. A., Tedder T. F. Neutrophils, monocytes, and lymphocytes bind to cytokine-activated kidney glomerular endothelial cells through L-selectin (LAM-1) in vitro. J Immunol. 1992 Oct 1;149(7):2437–2444. [PubMed] [Google Scholar]
- Chapman J. R., Ruben Z., Butchko G. M. Histology of and quantitative assays for oxazolone-induced allergic contact dermatitis in mice. Am J Dermatopathol. 1986 Apr;8(2):130–138. doi: 10.1097/00000372-198604000-00007. [DOI] [PubMed] [Google Scholar]
- Chisholm P. L., Williams C. A., Lobb R. R. Monoclonal antibodies to the integrin alpha-4 subunit inhibit the murine contact hypersensitivity response. Eur J Immunol. 1993 Mar;23(3):682–688. doi: 10.1002/eji.1830230317. [DOI] [PubMed] [Google Scholar]
- Dawson J., Sedgwick A. D., Edwards J. C., Lees P. The monoclonal antibody MEL-14 can block lymphocyte migration into a site of chronic inflammation. Eur J Immunol. 1992 Jun;22(6):1647–1650. doi: 10.1002/eji.1830220646. [DOI] [PubMed] [Google Scholar]
- 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]
- Issekutz T. B. Dual inhibition of VLA-4 and LFA-1 maximally inhibits cutaneous delayed-type hypersensitivity-induced inflammation. Am J Pathol. 1993 Nov;143(5):1286–1293. [PMC free article] [PubMed] [Google Scholar]
- Knol E. F., Tackey F., Tedder T. F., Klunk D. A., Bickel C. A., Sterbinsky S. A., Bochner B. S. Comparison of human eosinophil and neutrophil adhesion to endothelial cells under nonstatic conditions. Role of L-selectin. J Immunol. 1994 Sep 1;153(5):2161–2167. [PubMed] [Google Scholar]
- Kudo C., Yamashita T., Araki A., Terashita M., Watanabe T., Atsumi M., Tamura M., Sendo F. Modulation of in vivo immune response by selective depletion of neutrophils using a monoclonal antibody, RP-3. I. Inhibition by RP-3 treatment of the priming and effector phases of delayed type hypersensitivity to sheep red blood cells in rats. J Immunol. 1993 May 1;150(9):3728–3738. [PubMed] [Google Scholar]
- Labow M. A., Norton C. R., Rumberger J. M., Lombard-Gillooly K. M., Shuster D. J., Hubbard J., Bertko R., Knaack P. A., Terry R. W., Harbison M. L. Characterization of E-selectin-deficient mice: demonstration of overlapping function of the endothelial selectins. Immunity. 1994 Nov;1(8):709–720. doi: 10.1016/1074-7613(94)90041-8. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Luscinskas F. W., Ding H., Lichtman A. H. P-selectin and vascular cell adhesion molecule 1 mediate rolling and arrest, respectively, of CD4+ T lymphocytes on tumor necrosis factor alpha-activated vascular endothelium under flow. J Exp Med. 1995 Mar 1;181(3):1179–1186. doi: 10.1084/jem.181.3.1179. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Luscinskas F. W., Kansas G. S., Ding H., Pizcueta P., Schleiffenbaum B. E., Tedder T. F., Gimbrone M. A., Jr Monocyte rolling, arrest and spreading on IL-4-activated vascular endothelium under flow is mediated via sequential action of L-selectin, beta 1-integrins, and beta 2-integrins. J Cell Biol. 1994 Jun;125(6):1417–1427. doi: 10.1083/jcb.125.6.1417. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mayadas T. N., Johnson R. C., Rayburn H., Hynes R. O., Wagner D. D. Leukocyte rolling and extravasation are severely compromised in P selectin-deficient mice. Cell. 1993 Aug 13;74(3):541–554. doi: 10.1016/0092-8674(93)80055-j. [DOI] [PubMed] [Google Scholar]
- 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]
- Picker L. J., Kishimoto T. K., Smith C. W., Warnock R. A., Butcher E. C. ELAM-1 is an adhesion molecule for skin-homing T cells. Nature. 1991 Feb 28;349(6312):796–799. doi: 10.1038/349796a0. [DOI] [PubMed] [Google Scholar]
- Pizcueta P., Luscinskas F. W. Monoclonal antibody blockade of L-selectin inhibits mononuclear leukocyte recruitment to inflammatory sites in vivo. Am J Pathol. 1994 Aug;145(2):461–469. [PMC free article] [PubMed] [Google Scholar]
- Rossiter H., van Reijsen F., Mudde G. C., Kalthoff F., Bruijnzeel-Koomen C. A., Picker L. J., Kupper T. S. Skin disease-related T cells bind to endothelial selectins: expression of cutaneous lymphocyte antigen (CLA) predicts E-selectin but not P-selectin binding. Eur J Immunol. 1994 Jan;24(1):205–210. doi: 10.1002/eji.1830240132. [DOI] [PubMed] [Google Scholar]
- Scheynius A., Camp R. L., Puré E. Reduced contact sensitivity reactions in mice treated with monoclonal antibodies to leukocyte function-associated molecule-1 and intercellular adhesion molecule-1. J Immunol. 1993 Jan 15;150(2):655–663. [PubMed] [Google Scholar]
- Silber A., Newman W., Sasseville V. G., Pauley D., Beall D., Walsh D. G., Ringler D. J. Recruitment of lymphocytes during cutaneous delayed hypersensitivity in nonhuman primates is dependent on E-selectin and vascular cell adhesion molecule 1. J Clin Invest. 1994 Apr;93(4):1554–1563. doi: 10.1172/JCI117134. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sligh J. E., Jr, Ballantyne C. M., Rich S. S., Hawkins H. K., Smith C. W., Bradley A., Beaudet A. L. Inflammatory and immune responses are impaired in mice deficient in intercellular adhesion molecule 1. Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8529–8533. doi: 10.1073/pnas.90.18.8529. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Spertini O., Luscinskas F. W., Gimbrone M. A., Jr, Tedder T. F. Monocyte attachment to activated human vascular endothelium in vitro is mediated by leukocyte adhesion molecule-1 (L-selectin) under nonstatic conditions. J Exp Med. 1992 Jun 1;175(6):1789–1792. doi: 10.1084/jem.175.6.1789. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Spertini O., Luscinskas F. W., Kansas G. S., Munro J. M., Griffin J. D., Gimbrone M. A., Jr, Tedder T. F. Leukocyte adhesion molecule-1 (LAM-1, L-selectin) interacts with an inducible endothelial cell ligand to support leukocyte adhesion. J Immunol. 1991 Oct 15;147(8):2565–2573. [PubMed] [Google Scholar]
- Tedder T. F., Matsuyama T., Rothstein D., Schlossman S. F., Morimoto C. Human antigen-specific memory T cells express the homing receptor (LAM-1) necessary for lymphocyte recirculation. Eur J Immunol. 1990 Jun;20(6):1351–1355. doi: 10.1002/eji.1830200622. [DOI] [PubMed] [Google Scholar]
- Tedder T. F., Penta A. C., Levine H. B., Freedman A. S. Expression of the human leukocyte adhesion molecule, LAM1. Identity with the TQ1 and Leu-8 differentiation antigens. J Immunol. 1990 Jan 15;144(2):532–540. [PubMed] [Google Scholar]
- 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]
- Xu H., Gonzalo J. A., St Pierre Y., Williams I. R., Kupper T. S., Cotran R. S., Springer T. A., Gutierrez-Ramos J. C. Leukocytosis and resistance to septic shock in intercellular adhesion molecule 1-deficient mice. J Exp Med. 1994 Jul 1;180(1):95–109. doi: 10.1084/jem.180.1.95. [DOI] [PMC free article] [PubMed] [Google Scholar]