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Adhesion Molecule-1 (Madcam-1) Under Flow Lymphocytes to Mucosal Addressin Cell -Mediated Adhesion of 7Β4 Α Stimulates Integri

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Adhesion Molecule-1 (Madcam-1) Under Flow Lymphocytes to Mucosal Addressin Cell -Mediated Adhesion of 7Β4 Α Stimulates Integri Secondary Lymphoid-Tissue Chemokine (SLC) Stimulates Integrin α4β7-Mediated Adhesion of Lymphocytes to Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1) Under Flow This information is current as of October 1, 2021. Russell K. Pachynski, Steve W. Wu, Michael D. Gunn and David J. Erle J Immunol 1998; 161:952-956; ; http://www.jimmunol.org/content/161/2/952 Downloaded from References This article cites 25 articles, 15 of which you can access for free at: http://www.jimmunol.org/content/161/2/952.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on October 1, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 1998 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Secondary Lymphoid-Tissue Chemokine (SLC) Stimulates a b Integrin 4 7-Mediated Adhesion of Lymphocytes to Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1) Under Flow1 Russell K. Pachynski,2* Steve W. Wu,2* Michael D. Gunn,† and David J. Erle3*‡ The attachment of leukocytes to the endothelium is a multistep process that depends upon a very rapid increase in the adhesive activity of leukocyte integrins. A pertussis toxin-sensitive pathway stimulates integrin-dependent lymphocyte adhesion to Peyer’s patch high endothelial venules in vivo, but the factors responsible for activating this pathway have not been identified previously. We now report that secondary lymphoid-tissue chemokine (SLC) (also known as 6Ckine, Exodus-2, and thymus-derived chemo- tactic agent 4), a recently described CC chemokine that is expressed in Peyer’s patches and lymph nodes, rapidly activates Downloaded from integrin-mediated lymphocyte adhesion. Immobilized SLC increased the adhesion of HUT-78 T cells and human PBLs to mucosal addressin cell adhesion molecule-1, a protein that is expressed on Peyer’s patch and mesenteric lymph node high endothelial a b venules. This effect of SLC was seen in both static and flow chamber adhesion assays, was mediated by integrin 4 7, and was inhibited by pertussis toxin. The other CC chemokines tested did not increase adhesion to mucosal addressin cell adhesion molecule-1. SLC had a greater effect on naive CD41 T cells than on memory CD41 T cells; CD81 T cells, B cells, and NK cells were also responsive to SLC. SLC is likely to play an important role in regulating the recruitment of lymphocytes to Peyer’s http://www.jimmunol.org/ patches and lymph nodes. The Journal of Immunology, 1998, 161: 952–956. he attachment of blood leukocytes to the endothelium in- cell adhesion molecule-1 (MAdCAM-1). MAdCAM-1 that is pu- volves a series of tightly regulated adhesive interactions rified from murine Peyer’s patch HEVs has binding sites for both (1, 2). Initial attachment (tethering and rolling) is primar- L-selectin and integrin a b and can support both initial attach- T 4 7 a b ily mediated by interactions between selectins and their ligands. ment and rolling (via either L-selectin or 4 7) and firm arrest (via , a b a b Firm arrest often occurs within 1 s and is dependent upon the 4 7) (7, 8). 4 7 tends to support transient “stop and go” or binding of leukocyte integrins to Ig superfamily members which skipping interactions at low MAdCAM-1 density as well as rolling by guest on October 1, 2021 m a b are expressed on the endothelium. The firm arrest step depends (typically at 1–5 m/s) at higher MAdCAM-1 density (8). 4 7- upon a very rapid increase in the adhesive activity of integrins. For mediated firm adhesion can be stimulated by various nonphysi- 21 neutrophils, the binding of IL-8 or other chemokines to Gai pro- ologic stimuli, including phorbol esters and Mn (8–11). Heter- tein-coupled receptors initiates a pertussis toxin-sensitive signal; ologously expressed chemokine receptors and other Gai-coupled a b a b this signal results in a rapid increase in integrin L 2 (LFA-1)- receptors can also lead to a rapid and robust activation of 4 7 and mediated attachment to the endothelial ligand ICAM-1. Chemo- other integrins on lymphocyte cell lines (12). However, although kines can be immobilized on the endothelial surface by binding to some chemokines have been shown to induce increases in integrin- proteoglycans and other molecules, allowing for the effective ac- mediated lymphocyte adhesion using in vitro static adhesion as- tivation of intravascular leukocytes (3, 4). says (3, 13–15), these effects do not appear to be sufficiently rapid The adhesion of lymphocytes to Peyer’s patch high endothelial or robust enough to account for the intravascular firm arrest of 4 venules (HEVs) also depends upon a pertussis toxin-sensitive in- lymphocytes in HEVs. Furthermore, these chemokines are not tegrin activation step (5, 6). Ig superfamily members expressed on characteristically produced in Peyer’s patches or lymph Peyer’s patch HEVs include both ICAM-1 and mucosal addressin node HEVs. Secondary lymphoid-tissue chemokine (SLC) (also known as 6Ckine, Exodus-2, and thymus-derived chemotactic agent 4) is a *Lung Biology Center, Department of Medicine, †Cardiovascular Research Institute, recently described member of the CC chemokine family (16–20). and ‡Program in Immunology, University of California, San Francisco, CA 94143 SLC differs from most other CC chemokines in structure, chro- Received for publication January 12, 1998. Accepted for publication March 16, 1998. mosomal localization, pattern of tissue expression, and receptor The costs of publication of this article were defrayed in part by the payment of page usage. SLC mRNA is present at high levels in secondary lymphoid charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. tissues, including lymph nodes, the appendix, and Peyer’s patches. 1 This study was supported in part by National Institutes of Health Grant HL50024 In situ hybridization revealed an intense expression of SLC in and by a research grant from the Crohn’s and Colitis Foundation of America. HEV endothelial cells (20). Whereas most other known CC che- 2 R.K.P. and S.W.W. contributed equally to this report. mokines act predominantly on monocytes, SLC is chemotactic for 3 Address correspondence and reprint requests to Dr. David J. Erle, UCSF Box 0854, lymphocytes but not for monocytes (16–18). Gunn et al. (20) as- University of California, San Francisco, CA 94143-0854. E-mail address: sessed the effect of SLC on a b -dependent adhesion by allowing [email protected] L 2 lymphocytes to adhere to ICAM-1 under static conditions and then 4 Abbreviations used in this paper: HEV, high endothelial venule; MAdCAM-1, mu- cosal addressin cell adhesion molecule-1; rMAdCAM-1, recombinant soluble MAd- applying shear force to detach the cells (shear detachment assay). CAM-1 fusion protein; SLC, secondary lymphoid-tissue chemokine. Stimulating the cells with SLC for 12 min increased the number of Copyright © 1998 by The American Association of Immunologists 0022-1767/98/$02.00 The Journal of Immunology 953 cells that remained attached to ICAM-1, suggesting that SLC may otherwise noted) and perfused through the chamber. The calculated wall shear play a role in lymphocyte homing. To determine whether SLC stress was 2.0 dynes/cm2 (assuming viscosity equaled 0.01 poise) unless oth- could help account for the rapid intravascular firm arrest of lym- erwise noted. Images were captured using a TMS microscope (Nikon, Garden City, NJ), a charge-coupled device video camera (Sony, Park Ridge, NJ), and phocytes in Peyer’s patch HEVs, we analyzed the effects of SLC a videotape recorder (Panasonic, Secaucus, NJ). After 3 min of perfusion, each on the adhesion of lymphocytes to MAdCAM-1 under static and region was scanned, and attached (rolling plus arrested) cells were counted. At flow conditions. Here, we report that SLC, unlike other chemo- least eight 0.5-mm2 fields from each region were counted in each assay. The kines tested, was a potent and very rapid inducer of a b -mediated markings previously made on the back of each slide could be visualized with 4 7 the microscope and were used to accurately locate the regions coated with adhesion that markedly enhanced the attachment of lymphocytes MAdCAM-1 alone or with MAdCAM-1 plus chemokine. to MAdCAM-1 under flow. For Ab inhibition studies, cells were preincubated for 15 min at room a b temperature in adhesion assay buffer alone, in buffer containing anti- 4 7 m b m Materials and Methods Ab (Act-1, 20 g/ml), or in buffer containing anti- 2 Ab (CD18, 23 g/ Cells ml). To determine the effect of pertussis toxin, cells were treated with intact pertussis toxin (a gift of Dr. B. Conklin, University of California, San The human T lymphoma cell line HUT-78 (TIB 161; American Type Culture Francisco) or the pertussis toxin B protomer (List Biologic Laboratories, Collection, Manassas, VA) was maintained as described previously (10). Hu- Campbell, CA) at 100 ng/ml for2hat37°C before use. man PBLs were purified by density gradient centrifugation (Ficoll; Sigma, St.
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