L-selectin (LAM-1, LEC-CAM-1, Leu-8, TQ1) is a member of the selectin family of adhesion proteins that is expressed on the surface of circulating neutrophils, monocytes, eosinophils, basophils and certain lymphocytes (1-3). Both in vivo (4-6) and in vitro (7-10) studies have indicated a role for L-selectin in mediating the initial interaction between circulating blood leukocytes and the activated endothelium under flow. Although neutrophil and lymphocyte adhesive interactions have received considerable study, much less is known about monocyte-endothelial interactions. Preliminary studies by the applicant, using a simple """"""""non- static"""""""" (rotation) adhesion assay, have demonstrated that L-selectin interacting with its inducible endothelial ligand is involved in the initial contact between human blood monocytes and TNF- or lL-4-activated HUVEC (10,11). The overall objectives of this project are to study monocyte adhesion to endothelium in various states of activation, focusing on L-selectin and its inducible endothelial ligand using a recently developed in vitro flow model, and in vivo, in an murine model of inflammation; to understand the interrelationship of this adhesion pathway with other recently characterized inducible endothelial mechanisms; and to molecularly define the peripheral vascular endothelial (i.e., non- lymphoid) ligand(s) that support L-selectin-dependent monocyte attachment under flow.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
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Brigham and Women's Hospital
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Zahr, Alisar; Alcaide, Pilar; Yang, Jinling et al. (2016) Endomucin prevents leukocyte-endothelial cell adhesion and has a critical role under resting and inflammatory conditions. Nat Commun 7:10363
Venkatesh, Deepak; Mruk, Dolores; Herter, Jan M et al. (2016) AKAP9, a Regulator of Microtubule Dynamics, Contributes to Blood-Testis Barrier Function. Am J Pathol 186:270-84
Milstone, David S; Ilyama, Motoi; Chen, Mian et al. (2015) Differential role of an NF-?B transcriptional response element in endothelial versus intimal cell VCAM-1 expression. Circ Res 117:166-77
Cullere, Xavier; Plovie, Eva; Bennett, Paul M et al. (2015) The cerebral cavernous malformation proteins CCM2L and CCM2 prevent the activation of the MAP kinase MEKK3. Proc Natl Acad Sci U S A 112:14284-9
Luscinskas, Francis W; Imhof, Beat A (2014) Introduction for the special issue on new paradigms in leukocyte trafficking, lessons for therapeutics. Semin Immunopathol 36:133-6
Brown, Jonathan D; Lin, Charles Y; Duan, Qiong et al. (2014) NF-?B directs dynamic super enhancer formation in inflammation and atherogenesis. Mol Cell 56:219-231
Mayadas, Tanya N; Cullere, Xavier; Lowell, Clifford A (2014) The multifaceted functions of neutrophils. Annu Rev Pathol 9:181-218
Massaad, Michel J; Oyoshi, Michiko K; Kane, Jennifer et al. (2014) Binding of WIP to actin is essential for T cell actin cytoskeleton integrity and tissue homing. Mol Cell Biol 34:4343-54
Leick, Marion; Azcutia, Veronica; Newton, Gail et al. (2014) Leukocyte recruitment in inflammation: basic concepts and new mechanistic insights based on new models and microscopic imaging technologies. Cell Tissue Res 355:647-56
Azcutia, Veronica; Routledge, Matthew; Williams, Marcie R et al. (2013) CD47 plays a critical role in T-cell recruitment by regulation of LFA-1 and VLA-4 integrin adhesive functions. Mol Biol Cell 24:3358-68

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