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Title: | Leukocyte tetraspanin CD53 restrains alpha3integrin mobilization and facilitates cytoskeletal remodeling and transmigration in mice. | Authors: | Wright M.D.;Dankers W.;Elgass K.D.;Wicks I.P.;Kwok H.F.;Hickey M.J.;Yeung L.;Anderson J.M.L.;Wee J.L.;Demaria M.C.;Finsterbusch M.;Liu Y.S.;Hall P.;Smith B.C. | Monash Health Department(s): | Monash University - Monash School of Medicine | Institution: | (Yeung, Anderson, Wee, Finsterbusch, Liu, Hall, Smith, Dankers, Hickey) Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Clayton, VIC 3168, Australia (Yeung, Wee, Demaria, Wright) Department of Immunology, Monash University, Alfred Research Alliance, Melbourne, VIC 3004, Australia (Elgass) Monash Micro Imaging, Monash University, Clayton, VIC 3800, Australia (Wicks) Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia (Wicks) Department of Medical Biology, University of Melbourne, Parkville, VIC 3050, Australia (Wicks) Department of Rheumatology, Royal Melbourne Hospital, Parkville, VIC 3050, Australia (Kwok) Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macao | Issue Date: | 6-Aug-2020 | Copyright year: | 2020 | Publisher: | American Association of Immunologists (9650 Rockville Pike, Bethesda MD 20814, United States) | Place of publication: | United States | Publication information: | Journal of Immunology. 205 (2) (pp 521-532), 2020. Date of Publication: 15 Jul 2020. | Journal: | Journal of Immunology | Abstract: | The importance of tetraspanin proteins in regulating migration has been demonstrated in many diverse cellular systems. However, the function of the leukocyte-restricted tetraspanin CD53 remains obscure. We therefore hypothesized that CD53 plays a role in regulating leukocyte recruitment and tested this hypothesis by examining responses of CD53-deficient mice to a range of inflammatory stimuli. Deletion of CD53 significantly reduced neutrophil recruitment to the acutely inflamed peritoneal cavity. Intravital microscopy revealed that in response to several inflammatory and chemotactic stimuli, absence of CD53 had only minor effects on leukocyte rolling and adhesion in postcapillary venules. In contrast, Cd53-/- mice showed a defect in leukocyte transmigration induced by TNF, CXCL1 and CCL2, and a reduced capacity for leukocyte retention on the endothelial surface under shear flow. Comparison of adhesion molecule expression in wild-type and Cd53-/- neutrophils revealed no alteration in expression of b2 integrins, whereas L-selectin was almost completely absent from Cd53-/- neutrophils. In addition, Cd53-/- neutrophils showed defects in activation-induced cytoskeletal remodeling and translocation to the cell periphery, responses necessary for efficient transendothelial migration, as well as increased a3 integrin expression. These alterations were associated with effects on inflammation, so that in Cd53-/- mice, the onset of neutrophil-dependent serum-induced arthritis was delayed. Together, these findings demonstrate a role for tetraspanin CD53 in promotion of neutrophil transendothelial migration and inflammation, associated with CD53-mediated regulation of L-selectin expression, attachment to the endothelial surface, integrin expression and trafficking, and cytoskeletal function.Copyright © 2020 by The American Association of Immunologists, Inc. | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.4049/jimmunol.1901054 | PubMed URL: | 32532837 [http://www.ncbi.nlm.nih.gov/pubmed/?term=32532837] | ISSN: | 0022-1767 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/29158 | Type: | Article | Subjects: | antigen function arthritis bone marrow cell cell function cell migration cellular distribution cytoskeleton endothelium intravital microscopy leukocyte leukocyte adherence leukocyte rolling neutrophil peritoneal cavity protein expression shear flow venule alpha3 integrin CD18 antigen CXCL1 chemokine L selectin leukocyte surface antigen CD53 monocyte chemotactic protein 1 tumor necrosis factor monocyte |
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