LEUKOCYTE TETRASPANIN CD53 RESTRAINS α3 INTEGRIN MOBILIZATION AND FACILITATES CYTOSKELETAL REMODELLING AND TRANSMIGRATION IN MICE

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	LEUKOCYTE TETRASPANIN CD53 RESTRAINS α3 INTEGRIN MOBILIZATION AND FACILITATES CYTOSKELETAL REMODELLING AND TRANSMIGRATION IN MICE
	Yeung, L.; Anderson, J. M. L.; Wee, J. L.; Demaria, M. C.; Finsterbusch, M.; Liu, Y. S.; Elgass, K.; Wicks, I. P.; Kwok, H. F.; Wright, M. D.; Hickey, M. J.
	2020-06-01
Source Publication	Journal of Immunology
ISSN	0022-1767
Pages	-----
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 hypothesised 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 beta-2 integrins, while L-selectin was almost completely absent from Cd53-/- neutrophils. In addition, Cd53-/- neutrophils showed defects in activation-induced cytoskeletal remodelling and translocation of the alpha-3 integrin to the cell periphery, responses necessary for efficient transendothelial migration, as well as increased alpha-3 integrin expression. These alterations were associated with alterations in inflammation in 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.
Keyword	Neutrophil Recruitment Inflammation
Language	英語English
The Source to Article	PB_Publication
PUB ID	47501
Document Type	Journal article
Collection	DEPARTMENT OF BIOMEDICAL SCIENCES
Corresponding Author	Hickey, M. J.
Recommended Citation GB/T 7714	Yeung, L.,Anderson, J. M. L.,Wee, J. L.,et al. LEUKOCYTE TETRASPANIN CD53 RESTRAINS α3 INTEGRIN MOBILIZATION AND FACILITATES CYTOSKELETAL REMODELLING AND TRANSMIGRATION IN MICE[J]. Journal of Immunology, 2020, -----.
APA	Yeung, L.., Anderson, J. M. L.., Wee, J. L.., Demaria, M. C.., Finsterbusch, M.., Liu, Y. S.., Elgass, K.., Wicks, I. P.., Kwok, H. F.., Wright, M. D.., & Hickey, M. J. (2020). LEUKOCYTE TETRASPANIN CD53 RESTRAINS α3 INTEGRIN MOBILIZATION AND FACILITATES CYTOSKELETAL REMODELLING AND TRANSMIGRATION IN MICE. Journal of Immunology, -----.
MLA	Yeung, L.,et al."LEUKOCYTE TETRASPANIN CD53 RESTRAINS α3 INTEGRIN MOBILIZATION AND FACILITATES CYTOSKELETAL REMODELLING AND TRANSMIGRATION IN MICE".Journal of Immunology (2020):-----.

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