Genomes and Genes
Gene Symbol: P selectin
Description: selectin, platelet
Alias: CD62P, GMP-140, Grmp, LECAM3, PADGEM, P-selectin, CD62 antigen-like family member P, granule membrane protein 140, leukocyte-endothelial cell adhesion molecule 3, platelet activation dependent granule-external membrane protein
Products: P selectin
- Veerman K, Williams M, Uchimura K, Singer M, Merzaban J, Naus S, et al. Interaction of the selectin ligand PSGL-1 with chemokines CCL21 and CCL19 facilitates efficient homing of T cells to secondary lymphoid organs. Nat Immunol. 2007;8:532-9 pubmed..Our data show involvement of PSGL-1 in facilitating the entry of T cells into secondary lymphoid organs, thereby demonstrating the bifunctional nature of this molecule. ..
- Hickey M, Granger D, Kubes P. Molecular mechanisms underlying IL-4-induced leukocyte recruitment in vivo: a critical role for the alpha 4 integrin. J Immunol. 1999;163:3441-8 pubmed
- Ramos C, Huo Y, Jung U, Ghosh S, Manka D, Sarembock I, et al. Direct demonstration of P-selectin- and VCAM-1-dependent mononuclear cell rolling in early atherosclerotic lesions of apolipoprotein E-deficient mice. Circ Res. 1999;84:1237-44 pubmed
- Pan J, Xia L, Yao L, McEver R. Tumor necrosis factor-alpha- or lipopolysaccharide-induced expression of the murine P-selectin gene in endothelial cells involves novel kappaB sites and a variant activating transcription factor/cAMP response element. J Biol Chem. 1998;273:10068-77 pubmed..The presence of these elements in the murine, but not the human, P-selectin gene may explain in part why TNF-alpha or LPS stimulates transcription of P-selectin in a species-specific manner. ..
- Ridger V, Hellewell P, Norman K. L- and P-selectins collaborate to support leukocyte rolling in vivo when high-affinity P-selectin-P-selectin glycoprotein ligand-1 interaction is inhibited. Am J Pathol. 2005;166:945-52 pubmed..Together these data suggest that leukocytes can continue to roll in the absence of optimal P-selectin/PSGL-1 interaction using an alternative mechanism that involves P-selectin-, L-selectin-, and sLe(x)-bearing ligands. ..
- Lukacs N, John A, Berlin A, Bullard D, Knibbs R, Stoolman L. E- and P-selectins are essential for the development of cockroach allergen-induced airway responses. J Immunol. 2002;169:2120-5 pubmed..The findings indicate that both P- and E-selectin contribute to CRA-induced peribronchial inflammation and airway hyperreactivity. ..
- Robinson S, Frenette P, Rayburn H, Cummiskey M, Ullman Cullere M, Wagner D, et al. Multiple, targeted deficiencies in selectins reveal a predominant role for P-selectin in leukocyte recruitment. Proc Natl Acad Sci U S A. 1999;96:11452-7 pubmed..Data from the ELP(-/-) mice indicate, however, that all three selectins are important to leukocyte homeostasis and efficient neutrophil recruitment. ..
- Ellies L, Tsuboi S, Petryniak B, Lowe J, Fukuda M, Marth J. Core 2 oligosaccharide biosynthesis distinguishes between selectin ligands essential for leukocyte homing and inflammation. Immunity. 1998;9:881-90 pubmed..These studies indicate that core 2 oligosaccharide biosynthesis segregates the physiologic roles of selectins and reveal a function for the C2 GlcNAcT in myeloid homeostasis and inflammation. ..
- Petri B, Broermann A, Li H, Khandoga A, Zarbock A, Krombach F, et al. von Willebrand factor promotes leukocyte extravasation. Blood. 2010;116:4712-9 pubmed publisher..This step could be related to leukocyte diapedesis facilitated by destabilization of the endothelial barrier. ..
- Sanders W, Wilson R, Ballantyne C, Beaudet A. Molecular cloning and analysis of in vivo expression of murine P-selectin. Blood. 1992;80:795-800 pubmed..After administration of endotoxin, the highest levels of mRNA expression were detected in liver, lung, kidney, and heart. ..
- Rossi F, Corbel S, Merzaban J, Carlow D, Gossens K, Duenas J, et al. Recruitment of adult thymic progenitors is regulated by P-selectin and its ligand PSGL-1. Nat Immunol. 2005;6:626-34 pubmed..Furthermore, the number of resident thymic progenitors controls thymic expression of P-selectin, suggesting that regulation of P-selectin expression by a thymic 'niche occupancy sensor' may be used to direct progenitor access. ..
- Staite N, Justen J, Sly L, Beaudet A, Bullard D. Inhibition of delayed-type contact hypersensitivity in mice deficient in both E-selectin and P-selectin. Blood. 1996;88:2973-9 pubmed..Both P- and E-selectin are likely to play important roles in the development and maintenance of inflammatory diseases. ..
- Bullard D, Kunkel E, Kubo H, Hicks M, Lorenzo I, Doyle N, et al. Infectious susceptibility and severe deficiency of leukocyte rolling and recruitment in E-selectin and P-selectin double mutant mice. J Exp Med. 1996;183:2329-36 pubmed..These mice provide strong evidence for the functional importance of selectins in vivo. ..
- Zarbock A, Lowell C, Ley K. Spleen tyrosine kinase Syk is necessary for E-selectin-induced alpha(L)beta(2) integrin-mediated rolling on intercellular adhesion molecule-1. Immunity. 2007;26:773-83 pubmed..This identifies a second neutrophil-activation pathway that is as important as activation through G protein-coupled receptors (GPCRs). ..
- Sligh J, Ballantyne C, Rich S, Hawkins H, Smith C, Bradley A, et al. Inflammatory and immune responses are impaired in mice deficient in intercellular adhesion molecule 1. Proc Natl Acad Sci U S A. 1993;90:8529-33 pubmed..These mutant animals will be extremely valuable for examining the role of ICAM-1 and its counterreceptors in inflammatory disease processes and atherosclerosis. ..
- Weller A, Isenmann S, Vestweber D. Cloning of the mouse endothelial selectins. Expression of both E- and P-selectin is inducible by tumor necrosis factor alpha. J Biol Chem. 1992;267:15176-83 pubmedE-selectin (ELAM-1) and P-selectin (GMP-140, PADGEM, CD62) have both been described as human endothelial cell adhesion molecules for neutrophils and monocytes...
- Bullard D, Mobley J, Justen J, Sly L, Chosay J, Dunn C, et al. Acceleration and increased severity of collagen-induced arthritis in P-selectin mutant mice. J Immunol. 1999;163:2844-9 pubmed
- Kulidjian A, Issekutz A, Issekutz T. Differential role of E-selectin and P-selectin in T lymphocyte migration to cutaneous inflammatory reactions induced by cytokines. Int Immunol. 2002;14:751-60 pubmed..The relative contribution of the selectins varies depending on the initiating inflammatory stimulus and the genetic background. ..
- Li Z, Burns A, Rumbaut R, Smith C. gamma delta T cells are necessary for platelet and neutrophil accumulation in limbal vessels and efficient epithelial repair after corneal abrasion. Am J Pathol. 2007;171:838-45 pubmed..These results are consistent with the conclusion that gammadelta T cells are necessary for efficient inflammation, platelet localization in the limbus, and epithelial wound healing after corneal abrasion. ..
- Andre P, Hartwell D, Hrachovinova I, Saffaripour S, Wagner D. Pro-coagulant state resulting from high levels of soluble P-selectin in blood. Proc Natl Acad Sci U S A. 2000;97:13835-40 pubmed..We propose that sP-sel should no longer be considered only as a marker of inflammation or platelet activation, but also as a direct inducer of pro-coagulant activity associated with vascular and thrombotic diseases. ..
- Falati S, Liu Q, Gross P, Merrill Skoloff G, Chou J, Vandendries E, et al. Accumulation of tissue factor into developing thrombi in vivo is dependent upon microparticle P-selectin glycoprotein ligand 1 and platelet P-selectin. J Exp Med. 2003;197:1585-98 pubmed..We propose that PSGL-1 plays a role in blood coagulation in addition to its known role in leukocyte trafficking. ..
- Kunkel E, Jung U, Bullard D, Norman K, Wolitzky B, Vestweber D, et al. Absence of trauma-induced leukocyte rolling in mice deficient in both P-selectin and intercellular adhesion molecule 1. J Exp Med. 1996;183:57-65 pubmed..This severe defect in leukocyte rolling may explain the absence of leukocyte recruitment into the inflamed peritoneal cavity of P-selectin/ICAM-1-deficient mice at early time points (< or = 4 h). ..
- Gossens K, Naus S, Corbel S, Lin S, Rossi F, Kast J, et al. Thymic progenitor homing and lymphocyte homeostasis are linked via S1P-controlled expression of thymic P-selectin/CCL25. J Exp Med. 2009;206:761-78 pubmed publisher..Our findings suggest a model whereby thymic TCP importation is controlled by both early thymic niche occupancy and the peripheral lymphocyte pool via S1P. ..
- Kisucka J, Chauhan A, Zhao B, Patten I, Yesilaltay A, Krieger M, et al. Elevated levels of soluble P-selectin in mice alter blood-brain barrier function, exacerbate stroke, and promote atherosclerosis. Blood. 2009;113:6015-22 pubmed publisher..Thus, elevated sP-selectin is not only a biomarker for vascular disease, but also may contribute directly to atherosclerosis and cerebrovascular complications. ..
- Subramaniam M, Frenette P, Saffaripour S, Johnson R, Hynes R, Wagner D. Defects in hemostasis in P-selectin-deficient mice. Blood. 1996;87:1238-42 pubmed..This was also confirmed by measuring the radioactivity in the skin using chromium-labeled red blood cells. Therefore, it is evident that P-selectin plays a role in hemostasis as suggested by its support of platelet rolling. ..
- Walter U, Ayer L, Wolitzky B, Wagner D, Hynes R, Manning A, et al. Characterization of a novel adhesion function blocking monoclonal antibody to rat/mouse P-selectin generated in the P-selectin-deficient mouse. Hybridoma. 1997;16:249-57 pubmed..This novel MAb should be useful for studying P-selectin function in vitro and in vivo in both rat and mouse inflammation models. ..
- Jung U, Ramos C, Bullard D, Ley K. Gene-targeted mice reveal importance of L-selectin-dependent rolling for neutrophil adhesion. Am J Physiol. 1998;274:H1785-91 pubmed..We conclude that L-selectin can mediate rolling that results in sufficient leukocyte recruitment to account for the robust inflammatory response seen in E-/P- mice at later times. ..
- Zarbock A, Singbartl K, Ley K. Complete reversal of acid-induced acute lung injury by blocking of platelet-neutrophil aggregation. J Clin Invest. 2006;116:3211-9 pubmed..The key findings were confirmed in a sepsis-induced model of ALI. These findings may translate into improved clinical treatments for ALI. ..
- Atkinson C, Zhu H, Qiao F, Varela J, Yu J, Song H, et al. Complement-dependent P-selectin expression and injury following ischemic stroke. J Immunol. 2006;177:7266-74 pubmed
- Pelletier S, Hong D, Hu Y, Liu Y, Li S. Lack of the adhesion molecules P-selectin and intercellular adhesion molecule-1 accelerate the development of BCR/ABL-induced chronic myeloid leukemia-like myeloproliferative disease in mice. Blood. 2004;104:2163-71 pubmed
- Broide D, Sullivan S, Gifford T, Sriramarao P. Inhibition of pulmonary eosinophilia in P-selectin- and ICAM-1-deficient mice. Am J Respir Cell Mol Biol. 1998;18:218-25 pubmed..These studies suggest an important role for ICAM-1 and P-selectin in eosinophil recruitment to the lung after allergen challenge. ..
- Vandendries E, Hamilton J, Coughlin S, Furie B, Furie B. Par4 is required for platelet thrombus propagation but not fibrin generation in a mouse model of thrombosis. Proc Natl Acad Sci U S A. 2007;104:288-92 pubmed
- Manka D, Collins R, Ley K, Beaudet A, Sarembock I. Absence of p-selectin, but not intercellular adhesion molecule-1, attenuates neointimal growth after arterial injury in apolipoprotein e-deficient mice. Circulation. 2001;103:1000-5 pubmed..These findings demonstrate that the complete absence of P-selectin, but not ICAM-1, markedly reduces plaque area and suggest that P-selectin is critical for monocyte recruitment to sites of neointima formation after arterial injury. ..
- Norman K, Katopodis A, Thoma G, Kolbinger F, Hicks A, Cotter M, et al. P-selectin glycoprotein ligand-1 supports rolling on E- and P-selectin in vivo. Blood. 2000;96:3585-91 pubmed..The results suggest that P-selectin-PSGL-1 interaction alone is sufficient to mediate rolling in vivo and that E-selectin-PSGL-1 interaction supports slow rolling. ..
- Verdrengh M, Erlandsson Harris H, Tarkowski A. Role of selectins in experimental Staphylococcus aureus-induced arthritis. Eur J Immunol. 2000;30:1606-13 pubmed..aureus-induced arthritis: on the one hand, blockade of these selectins leads to less severe arthritic lesions in the initial stage of the disease; on the other, delayed recruitment of phagocytes decreases the clearance of bacteria. ..
- Kohler S, Ullrich S, Richter U, Schumacher U. E-/P-selectins and colon carcinoma metastasis: first in vivo evidence for their crucial role in a clinically relevant model of spontaneous metastasis formation in the lung. Br J Cancer. 2010;102:602-9 pubmed publisher..As the human HT 29 colon cancer cells are positive for the lectin Helix pomatia agglutinin (HPA), which identified the metastatic phenotype in earlier clinical studies, these results are of particular clinical relevance. ..
- Pan J, Xia L, McEver R. Comparison of promoters for the murine and human P-selectin genes suggests species-specific and conserved mechanisms for transcriptional regulation in endothelial cells. J Biol Chem. 1998;273:10058-67 pubmed..These data suggest that both species-specific and conserved mechanisms regulate transcription of the human and murine P-selectin genes. ..
- Stübke K, Wicklein D, Herich L, Schumacher U, Nehmann N. Selectin-deficiency reduces the number of spontaneous metastases in a xenograft model of human breast cancer. Cancer Lett. 2012;321:89-99 pubmed publisher..However, spontaneous metastasis was not completely abrogated, hence additional cell adhesion molecules must be involved in the metastatic spread. ..
- Rosenkranz A, Mendrick D, Cotran R, Mayadas T. P-selectin deficiency exacerbates experimental glomerulonephritis: a protective role for endothelial P-selectin in inflammation. J Clin Invest. 1999;103:649-59 pubmed..Thus, the protective effect in wild-type mice may be accounted for, in part by soluble P-selectin shed by non-renal endothelial cells, although other endothelial P-selectin-dependent mechanisms cannot be ruled out. ..
- Xia L, Ramachandran V, McDaniel J, Nguyen K, Cummings R, McEver R. N-terminal residues in murine P-selectin glycoprotein ligand-1 required for binding to murine P-selectin. Blood. 2003;101:552-9 pubmed..Because it uses only one tyrosine, murine PSGL-1 may rely more on other peptide components and O-glycosylation to bind to P-selectin than does human PSGL-1. ..
- Frenette P, Mayadas T, Rayburn H, Hynes R, Wagner D. Susceptibility to infection and altered hematopoiesis in mice deficient in both P- and E-selectins. Cell. 1996;84:563-74 pubmed..Our results show that the absence of endothelial selectins severely affects leukocyte homeostasis and indicate that these two selectins are as important for normal leukocyte function as are the leukocyte beta2 integrins...
- Hwang J, Yamanouchi J, Santamaria P, Kubes P. A critical temporal window for selectin-dependent CD4+ lymphocyte homing and initiation of late-phase inflammation in contact sensitivity. J Exp Med. 2004;199:1223-34 pubmed
- Lam F, Burns A, Smith C, Rumbaut R. Platelets enhance neutrophil transendothelial migration via P-selectin glycoprotein ligand-1. Am J Physiol Heart Circ Physiol. 2011;300:H468-75 pubmed publisher..These data support the notion that platelets enhance neutrophil transmigration across the inflamed endothelium both in vivo and in vitro, via a PSGL-1-dependent mechanism. ..
- Gironella M, Molla M, Salas A, Soriano A, Sans M, Closa D, et al. The role of P-selectin in experimental colitis as determined by antibody immunoblockade and genetically deficient mice. J Leukoc Biol. 2002;72:56-64 pubmed..Therefore, ablation of P-selectin function ameliorates colitis, but this protection is attenuated in P-selectin(-/-) mice, probably due to compensatory mechanisms that involve up-regulation of other adhesion molecules such as VCAM-1. ..
- Li Z, Burns A, Smith C. Two waves of neutrophil emigration in response to corneal epithelial abrasion: distinct adhesion molecule requirements. Invest Ophthalmol Vis Sci. 2006;47:1947-55 pubmed..The first is dependent on CD18 integrins and selectins, whereas the second is CD18-independent but requires selectins. Early leukocyte emigration appears to promote re-epithelialization. ..
- Wang H, Wang J, Zhang L, Geng Z, Xu W, Xu T, et al. P-selectin primes leukocyte integrin activation during inflammation. Nat Immunol. 2007;8:882-92 pubmed..Our data demonstrate the functional importance of this newly identified signaling pathway mediated by P-selectin glycoprotein ligand 1. ..
- Larbi K, Dangerfield J, Culley F, Marshall D, Haskard D, Jose P, et al. P-selectin mediates IL-13-induced eosinophil transmigration but not eotaxin generation in vivo: a comparative study with IL-4-elicited responses. J Leukoc Biol. 2003;73:65-73 pubmed..In conclusion, the regulatory role of P-selectin in leukocyte transmigration elicited by IL-13 appears to be tissue-specific, a phenomenon that is independent of the ability of the cytokine to stimulate eotaxin generation. ..
- Burch E, Shinde Patil V, Camphausen R, Kiani M, Goetz D. The N-terminal peptide of PSGL-1 can mediate adhesion to trauma-activated endothelium via P-selectin in vivo. Blood. 2002;100:531-8 pubmed..ek.Fc microspheres with a monoclonal antibody to PSGL-1. Combined, the results indicate that the N-terminal peptide of PSGL-1 can mediate adhesion to trauma-activated microvascular endothelium via P-selectin in vivo. ..
- Lawson J, Burns A, Farhood A, Lynn Bajt M, Collins R, Smith C, et al. Pathophysiologic importance of E- and L-selectin for neutrophil-induced liver injury during endotoxemia in mice. Hepatology. 2000;32:990-8 pubmed..Therefore, we conclude that blocking E-selectin or eliminating this gene may have protected against Gal/ET-induced liver injury in vivo by inhibiting the full activation of neutrophils during the transmigration process. ..
- Bartholdy C, Marker O, Thomsen A. Migration of activated CD8(+) T lymphocytes to sites of viral infection does not require endothelial selectins. Blood. 2000;95:1362-9 pubmed..Blood. 2000;95:1362-1369) ..
- Tang T, Frenette P, Hynes R, Wagner D, Mayadas T. Cytokine-induced meningitis is dramatically attenuated in mice deficient in endothelial selectins. J Clin Invest. 1996;97:2485-90 pubmed
- Pitchford S, Momi S, Giannini S, Casali L, Spina D, Page C, et al. Platelet P-selectin is required for pulmonary eosinophil and lymphocyte recruitment in a murine model of allergic inflammation. Blood. 2005;105:2074-81 pubmed..P-selectin expression on the surfaces of platelets is a major requirement for pulmonary eosinophil and lymphocyte recruitment, allowing circulating platelets to bind to and stimulate leukocytes for endothelial attachment. ..
- Nakatani K, Fujii H, Hasegawa H, Terada M, Arita N, Ito M, et al. Endothelial adhesion molecules in glomerular lesions: association with their severity and diversity in lupus models. Kidney Int. 2004;65:1290-300 pubmed..The severity and diversity of the histopathology of lupus nephritis are partially associated with the expression of vascular endothelial adhesion molecules in glomeruli. ..
- Smith M, Smith M, Lawrence M, Ley K. Viscosity-independent velocity of neutrophils rolling on p-selectin in vitro or in vivo. Microcirculation. 2002;9:523-36 pubmed..The stable rolling velocity allows sufficient surveillance of the endothelial surface, even in venules with high WSS. doi:10.1038/sj.mm.7800165 ..
- Bistrian R, Dorn A, Mobest D, Ruster B, Ludwig R, Scheele J, et al. Shear stress-mediated adhesion of acute myeloid leukemia and KG-1 cells to endothelial cells involves functional P-selectin. Stem Cells Dev. 2009;18:1235-42 pubmed publisher..Thus, the currently available data suggest a role of P- and E-selectin in coordinated circulation of AML cells. Thus, P- or E-selectin mediated adhesion of AML cells may provide a target for the development anti-leukemic therapies. ..
- Tomita H, Iwata Y, Ogawa F, Komura K, Shimizu K, Yoshizaki A, et al. P-selectin glycoprotein ligand-1 contributes to wound healing predominantly as a p-selectin ligand and partly as an e-selectin ligand. J Invest Dermatol. 2009;129:2059-67 pubmed publisher..These results suggest that PSGL-1 contributes to wound healing predominantly as a P-selectin ligand and partly as an E-selectin ligand by mediating infiltration of inflammatory cells. ..
- McCafferty D, Kanwar S, Granger D, Kubes P. E/P-selectin-deficient mice: an optimal mutation for abrogating antigen but not tumor necrosis factor-alpha-induced immune responses. Eur J Immunol. 2000;30:2362-71 pubmed..Although rolling and adhesion was dramatically blunted in P-selectin- or P selectin/ICAM-1-deficient mice, emigrated cell number was similar to that observed in wild-type mice...