Leukocyte trafficking into lymphoid tissues or sites of infection or injury is regulated by the coordinated expression of adhesion and signaling molecules [1, 2]. Binding of selecfins to glycoconjugate ligands mediates tethering and rolling on vascular surfaces. Binding of leukocyte integrins to Ig-like proteins slows rolling, promotes firm adhesion, and directs migration. Cytokines, thrombin, histamine, and other mediators inifiate leukocyte recruitment by stimulafing endothelial cells to express adhesion molecules and chemokines. Rolling leukocytes receive signals from engagement of selecfin ligands and chemokines that cause integrin-dependent deceleration, arrest, and migration. Combinatorial diversity of adhesion and signaling molecules controls the number and type of leukocytes recruited to a particular tissue, as well as the duration of the response. Dysregulated expression of these molecules contributes to tissue injury in inflammatory diseases.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL085607-09
Application #
8677945
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
9
Fiscal Year
2014
Total Cost
$592,566
Indirect Cost
$234,098
Name
Oklahoma Medical Research Foundation
Department
Type
DUNS #
077333797
City
Oklahoma City
State
OK
Country
United States
Zip Code
73104
Mehta-D'souza, Padmaja; Klopocki, Arkadiusz G; Oganesyan, Vaheh et al. (2017) Glycan Bound to the Selectin Low Affinity State Engages Glu-88 to Stabilize the High Affinity State under Force. J Biol Chem 292:2510-2518
Panicker, Sumith R; Mehta-D'souza, Padmaja; Zhang, Nan et al. (2017) Circulating soluble P-selectin must dimerize to promote inflammation and coagulation in mice. Blood 130:181-191
Liu, Zhenghui; Yago, Tadayuki; Zhang, Nan et al. (2017) L-selectin mechanochemistry restricts neutrophil priming in vivo. Nat Commun 8:15196
Bergstrom, Kirk; Liu, Xiaowei; Zhao, Yiming et al. (2016) Defective Intestinal Mucin-Type O-Glycosylation Causes Spontaneous Colitis-Associated Cancer in Mice. Gastroenterology 151:152-164.e11
Rahman, H N Ashiqur; Wu, Hao; Dong, Yunzhou et al. (2016) Selective Targeting of a Novel Epsin-VEGFR2 Interaction Promotes VEGF-Mediated Angiogenesis. Circ Res 118:957-969
Liu, Zhenghui; Zhang, Nan; Shao, Bojing et al. (2016) Replacing the Promoter of the Murine Gene Encoding P-selectin with the Human Promoter Confers Human-like Basal and Inducible Expression in Mice. J Biol Chem 291:1441-7
Brazil, Jennifer C; Sumagin, Ronen; Cummings, Richard D et al. (2016) Targeting of Neutrophil Lewis X Blocks Transepithelial Migration and Increases Phagocytosis and Degranulation. Am J Pathol 186:297-311
Chen, Wei-Sheng; Cao, Zhiyi; Sugaya, Satoshi et al. (2016) Pathological lymphangiogenesis is modulated by galectin-8-dependent crosstalk between podoplanin and integrin-associated VEGFR-3. Nat Commun 7:11302
Dong, Yunzhou; Wu, Hao; Rahman, H N Ashiqur et al. (2016) Motif mimetic of epsin perturbs tumor growth and metastasis. J Clin Invest 126:1607
Crosswhite, Patrick L; Podsiadlowska, Joanna J; Curtis, Carol D et al. (2016) CHD4-regulated plasmin activation impacts lymphovenous hemostasis and hepatic vascular integrity. J Clin Invest 126:2254-66

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