.Importance of Defining Pathways for Recruitment and Turnover of Leukocytes in Inflammation -Inflammation is an immune cell response that leads to the accumulation of white blood cells (leukocytes) at sites of infection, injury or irritation. The extravasation of polymorphonuclear leukocytes (PMNs), primarily neutrophils, through selectin and integrin-mediated pathways, to a site of inflammation is followed by the emigration of monocytes/macrophages (Fig. 1). Released granule proteins from activated neutrophils induce further emigration of inflammatory cells to such sites, involving selectins, P2-integrins and formyl-peptide receptors. Accompanying changes in the chemokine network create a favorable local microenvironment for extravasation of additional inflammatory monocytes. Thus, for this positive feedback loop to end, inflammation must be resolved by the removal of the inflammatory insult (bacteria or wound detritus), along with eventual removal of the emigrated inflammatory cells. While resolution is clearly the key to limiting tissue injury in all types of inflammation, it is remarkable that so little is known about the mechanism of cellular turnover and the factors promoting the resolution of inflammation. It has been thought that resolution occurs through spontaneous apoptosis of neutrophils and their subsequent phagocytosis and engulfment(4). Surprisingly, however, neutrophil apoptosis in vivo is not a major factor in regulating their numbers in inflammation. Unlike T cells, which accumulate following perturbation of pathways involved in leukocyte apoptosis(5,6), inhibition of neutrophil apoptosis does not greatly alter neutrophil turnover in vivo, but the mechanism(s) of targeting viable neutrophils for removal is unknown (5-8). Thus, neutrophil turnover is possibly regulated by nonapoptotic factors.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL085607-08
Application #
8469889
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
8
Fiscal Year
2013
Total Cost
$499,162
Indirect Cost
$56,927
Name
Oklahoma Medical Research Foundation
Department
Type
DUNS #
077333797
City
Oklahoma City
State
OK
Country
United States
Zip Code
73104
Herzog, Brett H; Fu, Jianxin; Xia, Lijun (2014) Mucin-type O-glycosylation is critical for vascular integrity. Glycobiology 24:1237-41
Sreeramkumar, Vinatha; Adrover, José M; Ballesteros, Ivan et al. (2014) Neutrophils scan for activated platelets to initiate inflammation. Science 346:1234-8
Stowell, Sean R; Arthur, Connie M; McBride, Ryan et al. (2014) Microbial glycan microarrays define key features of host-microbial interactions. Nat Chem Biol 10:470-6
Liu, Xiaolei; Pasula, Satish; Song, Hoogeun et al. (2014) Temporal and spatial regulation of epsin abundance and VEGFR3 signaling are required for lymphatic valve formation and function. Sci Signal 7:ra97
Wan, Xiang; Sato, Hidetaka; Miyaji, Hiromasa et al. (2013) Fucosyltransferase VII improves the function of selectin ligands on cord blood hematopoietic stem cells. Glycobiology 23:1184-91
Herzog, Brett H; Fu, Jianxin; Wilson, Stephen J et al. (2013) Podoplanin maintains high endothelial venule integrity by interacting with platelet CLEC-2. Nature 502:105-9
Shao, Bojing; Yago, Tadayuki; Coghill, Phillip A et al. (2012) Signal-dependent slow leukocyte rolling does not require cytoskeletal anchorage of P-selectin glycoprotein ligand-1 (PSGL-1) or integrin *L*2. J Biol Chem 287:19585-98
Miner, Jonathan J; Shao, Bojing; Wang, Ying et al. (2011) Cytoplasmic domain of P-selectin glycoprotein ligand-1 facilitates dimerization and export from the endoplasmic reticulum. J Biol Chem 286:9577-86
Shao, Bojing; Wahrenbrock, Mark G; Yao, Longbiao et al. (2011) Carcinoma mucins trigger reciprocal activation of platelets and neutrophils in a murine model of Trousseau syndrome. Blood 118:4015-23
Cerliani, Juan P; Stowell, Sean R; Mascanfroni, Ivan D et al. (2011) Expanding the universe of cytokines and pattern recognition receptors: galectins and glycans in innate immunity. J Clin Immunol 31:10-21

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