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Adhesion (Cd11b/CD18) in Regulating Neutrophil Mac-1/Complement Receptor Type 3 Function of the Lectin Domain Of

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Adhesion (Cd11b/CD18) in Regulating Neutrophil Mac-1/Complement Receptor Type 3 Function of the Lectin Domain Of Function of the Lectin Domain of Mac-1/Complement Receptor Type 3 (CD11b/CD18) in Regulating Neutrophil Adhesion This information is current as of September 25, 2021. Yu Xia, Gita Borland, Jibiao Huang, Ikuko F. Mizukami, Howard R. Petty, Robert F. Todd III and Gordon D. Ross J Immunol 2002; 169:6417-6426; ; doi: 10.4049/jimmunol.169.11.6417 http://www.jimmunol.org/content/169/11/6417 Downloaded from References This article cites 60 articles, 38 of which you can access for free at: http://www.jimmunol.org/content/169/11/6417.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 by guest on September 25, 2021 *average 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 © 2002 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Function of the Lectin Domain of Mac-1/Complement Receptor Type 3 (CD11b/CD18) in Regulating Neutrophil Adhesion1 Yu Xia,2* Gita Borland,* Jibiao Huang,† Ikuko F. Mizukami,‡ Howard R. Petty,† Robert F. Todd III,‡ and Gordon D. Ross3* A lectin function within CD11b mediates both cytotoxic priming of Mac-1/complement receptor type 3 (CR3) by ␤-glucan and the formation of transmembrane signaling complexes with GPI-anchored glycoproteins such as CD16b (Fc␥RIIIb). A requirement for GPI-anchored urokinase plasminogen activator receptor (uPAR; CD87) in neutrophil adhesion and diapedesis has been demon- strated with uPAR-knockout mice. In this study, neutrophil activation conditions generating high-affinity (H-AFN) or low-affinity ␤ (L-AFN) 2 integrin adhesion were explored. A role for the Mac-1/CR3 lectin domain and uPAR in mediating H-AFN or L-AFN adhesion was suggested by the inhibition of Mac-1/CR3-dependent adhesion to ICAM-1 or fibrinogen by ␤-glucan or anti-uPAR. The formation of uPAR complexes with Mac-1/CR3 activated for L-AFN adhesion was demonstrated by fluorescence resonance Downloaded from energy transfer. Conversely, Jurkat cell LFA-1 H-AFN-adhesion to ICAM-1 was not associated with uPAR/LFA-1 complexes, any requirement for GPI-anchored glycoproteins, or inhibition by ␤-glucan. A single CD11b lectin site for ␤-glucan and uPAR was suggested because the binding of either ␤-glucan or uPAR to Mac-1/CR3 selectively masked two CD11b epitopes adjacent to the transmembrane domain. Moreover, treatment with phosphatidylinositol-specific phospholipase C that removed GPI-anchored proteins increased CD11b-specific binding of 125I-labeled ␤-glucan by 3-fold and this was reversed with soluble recombinant uPAR. Conversely, neutrophil activation for generation of Mac-1/CR3/uPAR complexes inhibited CD11b-dependent binding of http://www.jimmunol.org/ 125I-labeled ␤-glucan by 75%. These data indicate that the same lectin domain within CD11b regulates both the cytotoxic and adhesion functions of Mac-1/CR3. The Journal of Immunology, 2002, 169: 6417–6426. ␣ ␤ he leukocyte M 2 integrin known also as Mac-1, com- can to a distinct lectin domain contained within the C-terminal plement receptor type 3 (CR3),4 and CD11b/CD18 func- region of CD11b (7–9). Ligation of fungal ␤(1, 3)-glucans to the T tions both as an adhesion molecule facilitating diapedesis lectin domain of CD11b results in priming of the receptor, such and as a C3R enabling phagocytosis or degranulation in response that yeast cells bound to the I-domain via iC3b trigger “outside-in” to factor I-cleaved C3b fragment of C3 (iC3b)-opsonized micro- signaling for phagocytosis or degranulation (10, 11). In addition, organisms (1–5). Important protein ligands such as ICAM-1, iC3b, the binding of soluble ␤-glucan or yeast cell walls to the lectin by guest on September 25, 2021 and fibrinogen bind to overlapping sites contained within an “in- domain can generate the H-AFN MIDAS conformation within the serted” I-domain at the N terminus of the CD11b subunit that is I-domain (11, 12). induced to express a high-affinity (H-AFN) metal ion-dependent Several lines of evidence indicate that adhesion via Mac-1/CR3 adhesion site (MIDAS) following cell activation. Notably, adhe- binding to endothelial cell ICAM-1 requires the formation of sion may also occur through the cytoskeleton-regulated clustering membrane complexes between Mac-1/CR3 and GPI-anchored of integrins that retain a low-affinity (L-AFN) binding site state urokinase plasminogen activator receptor (uPAR). mAbs to differ- (6). Phagocytosis of iC3b-opsonized fungi that are captured first by ent epitopes of uPAR can either inhibit or induce Mac-1-dependent the I-domain requires secondary ligation of fungal cell wall ␤-glu- adhesion, and removal of GPI-anchored proteins with phosphati- dylinositol-specific phospholipase C (PiPLC) (13) or inhibition of uPAR synthesis with an antisense oligonucleotide (14, 15) pre- *Chemoattractant Group of the James Graham Brown Cancer Center, Departments of vents Mac-1-dependent adhesion until the cells are reconstituted Pathology, and of Microbiology and Immunology, University of Louisville, Louis- ville, KY 40202; †Department of Biological Sciences, Wayne State University, De- with soluble recombinant uPAR (sr-uPAR) (13). Moreover, neu- troit, MI 48202; and ‡Division of Hematology/Oncology, Department of Internal trophils from uPAR-deficient mice exhibit defective diapedesis Medicine, Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109 into certain inflammatory sites (13, 16). A lectin-like interaction Received for publication May 9, 2002. Accepted for publication September 26, 2002. appears to be involved in uPAR-dependent adhesion because the surface complexes between uPAR and Mac-1 are disrupted by sug- The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance ars such as N-acetyl-D-glucosamine (NADG) (17). These data sug- with 18 U.S.C. Section 1734 solely to indicate this fact. gest that uPAR may bind to the same lectin domain within the C 1 This work was supported by National Institutes of Health Grants CA86412 (to terminus of CD11b that is used for cytotoxic degranulation in re- G.D.R.), CA42246 (to R.F.T.), and AI27409 (to H.R.P.). sponse to iC3b-opsonized yeast. Moreover, because similar sugar- 2 Current address: Celera, 180 Kimball Way, South San Francisco, CA 84080 inhibitable complexes have been observed between uPAR and 3 Address correspondence and reprint requests to Dr. Gordon D. Ross, James Graham ␤ ␤ CR4 (CD11c/CD18) (18), as well as between uPAR and 1 or 3 Brown Cancer Center, University of Louisville, 529 South Jackson Street, Room 429, Louisville, KY 40202. E-mail address: [email protected] integrins (19), it appears possible that lectin-dependent complexes formed with uPAR may be important for adhesion with a broad 4 Abbreviations used in this paper: CR3, complement receptor type 3; iC3b, factor I-cleaved C3b fragment of C3; H-AFN, high affinity; L-AFN, low affinity; MIDAS, range of integrins. Although sugar-inhibitable complexes between metal ion-dependent adhesion site; uPAR, urokinase plasminogen activator receptor; LFA-1 (CD11a/CD18) and Fc␥RIIIB have been demonstrated us- PiPLC, phosphatidylinositol-specific phospholipase C; sr-uPAR, soluble recombinant uPAR; NADG,N-acetyl-D-glucosamine; RET, resonance energy transfer; TRITC, ing resonance energy transfer (RET) techniques (20), the forma- tetramethylrhodamine isothiocyanate; 125I-␤-glucan, 125I-labeled ␤-glucan. tion of LFA-1 complexes with uPAR has not been investigated. Copyright © 2002 by The American Association of Immunologists, Inc. 0022-1767/02/$02.00 6418 LECTIN DOMAIN REGULATION OF Mac-1/CR3 ADHESION Nevertheless, other investigators have demonstrated the recovery All other chemicals and reagents, except where specified, were purchased of uPAR within anti-CD11a immunoprecipitates from monocytes, from Sigma-Aldrich (St. Louis, MO). as well as sparse LFA-1/uPAR cocapping (21). Neutrophils and T cells A lectin site has been identified in both human and murine CR3 that binds soluble or particulate ␤-glucan. However, studies of Peripheral blood neutrophils were isolated under LPS-free conditions using ␤ two-step Ficoll/Hypaque density gradient centrifugation (34). Peripheral other 2 integrins have failed to demonstrate a similar lectin ac- blood T lymphocytes were isolated using RosetteSep T Cell Enrichment tivity (8, 10, 22). The exact location of the lectin site within the C Cocktail according to the manufacturer’s protocol (StemCell Technologies, terminus of CD11b has not been determined, but its blockade by Vancouver, British Columbia, Canada). Isolated T cell preparations were ϩ ␤-glucan oligosaccharides containing as few as seven glucose sub- Ն96% CD3 , but only weak staining for uPAR was detectable by indirect units (23) suggests that it represents a relatively small portion of immunofluorescence. The T cell line Jurkat E6-1 was obtained
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