Disease relevance of SELP

• SELPLG and SELP single-nucleotide polymorphisms in multiple sclerosis [1].
• Specific binding of monocytes to venules lined by low or high endothelium occurred at concentrations as low as 5 x 10(5) cells/ml. mAbs specific for P-selectin (CD62, GMP-140/PADGEM) blocked adhesion by > 90% in all synovitis specimens examined [2].
• The present findings form the basis for investigating the role of GMP140 in tumor invasiveness and metastasis [3].
• Granule membrane protein 140 (GMP140) binds to carcinomas and carcinoma-derived cell lines [3].
• These data suggest that GMP-140, as well as ICAM-1, could play an important role in the initiation of MNC infiltration in Graves' disease [4].

Psychiatry related information on SELP

• There was no difference between subjects with PTSD and healthy control subjects in proportions of circulating lymphocyte subsets or in expression of the lymphocyte markers CD62, CD25, and CD45RO/CD45RA [5].
• To assess whether platelets are activated in transient global amnesia (TGA) and TIA, blood samples were analyzed by fluorescence-activated cytoscan using antibodies specific for platelet fibrinogen receptor (PAC1) and P-selectin (CD62P) [6].

High impact information on SELP

• This network of interactions includes three genes in the TGF-beta pathway and SELP, which is associated with stroke in the general population [7].
• The neutrophil selectin LECAM-1 presents carbohydrate ligands to the vascular selectins ELAM-1 and GMP-140 [8].
• Adhesion of resting or activated neutrophils through the integrins LFA-1 and Mac-1 to ICAM-1 in a lipid bilayer does not occur at physiologic shear stresses; however, static incubation of activated neutrophils allows development of adhesion that is greater than 100-fold more shear resistant than found on CD62 [9].
• Data presented to date suggest that one ligand of CD62 includes CD15 (Lewis x determinant) and sialic acid [10].
• Addition of a chemoattractant to activate LFA-1 and Mac-1 results in the arrest of neutrophils rolling on bilayers containing both CD62 and ICAM-1 [9].

Chemical compound and disease context of SELP

• MATERIALS AND METHODS: A hydrogel system composed of SELP/adenovirus mixture was prepared [11].
• Lipopolysaccharide from enterohemorrhagic Escherichia coli binds to platelets through TLR4 and CD62 and is detected on circulating platelets in patients with hemolytic uremic syndrome [12].
• RESULTS: Basal platelet expression of CD61, CD42a and CD62P, and adenosine diphosphate-stimulated CD62P expression were increased in women with preeclampsia compared with normotensive pregnant women [13].
• METHODS AND RESULTS: Platelet P-selectin (CD62) and activated GP IIb/IIIa (PAC-1) expression on platelet membrane was quantified in whole blood as well as platelet aggregation in platelet-rich plasma in 43 patients with unstable angina before and during treatment with UFH or enoxaparin [14].
• In vitro, hypothermia inhibited both thrombin- and U46619-induced upregulation of GMP-140, downregulation of the GPIb-IX complex, platelet aggregation, and TXB2 generation [15].

Biological context of SELP

• No significant differences in both SELP SNPs were found between patients and controls, whereas a decreased frequency of the Met62Ile SNP was found in patients versus controls in the Italian population (P = 0.025) [1].
• Cloning of GMP-140, a granule membrane protein of platelets and endothelium: sequence similarity to proteins involved in cell adhesion and inflammation [16].
• In situ hybridization mapped GMP-140 to human chromosome 1 bands 21-24 consistent with chromosomal localization of LHR [17].
• These data suggest that LHR, ELAM-1, and GMP-140 comprise an adhesion protein family, the selectins, that arose by multiple gene duplication events before divergence of mouse and human [17].
• PADGEM protein (PADGEM), also known as GMP140, is a platelet alpha-granule membrane protein that is translocated to the external membrane after platelet activation [18].

Anatomical context of SELP

• Three differentially expressed selectin genes (SELE, SELP, and SELL), important in the initial stages of leukocyte extravasation, have been reported in mammals [19].
• GMP-140 is an integral membrane glycoprotein found in secretory granules of platelets and endothelial cells [16].
• Granule membrane protein-140 (GMP-140), a membrane glycoprotein of platelet and endothelial cell secretory granules, is rapidly redistributed to the plasma membrane during cellular activation and degranulation [20].
• Also known as PADGEM protein, GMP-140 is structurally related to two molecules involved in leukocyte adhesion to vascular endothelium: ELAM-1, a cytokine-inducible endothelial cell receptor for neutrophils, and the MEL-14 lymphocyte homing receptor [20].
• Human neutrophils and promyelocytic HL-60 cells bind specifically to COS cells transfected with GMP-140 complementary DNA and to microtitre wells coated with purified GMP-140 [20].

Associations of SELP with chemical compounds

• Within minutes after stimulation with phorbol esters or histamine, human endothelial cells become adhesive for neutrophils; this interaction is inhibited by antibodies to GMP-140 [20].
• Recognition requires sialic acid, because cells expressing large amounts of Lewis x, but not sialyl Lewis x, do not interact with GMP-140 [21].
• Thus, the sialyl Lewis x tetrasaccharide may require additional structural modifications or specific presentations in order for leukocytes in flowing blood to interact rapidly and with high affinity to GMP-140 on activated platelets or endothelium [21].
• The interaction of PSGL-1 with P-selectin (CD62P) mediates tethering, rolling, and weak adhesion of leukocytes, during which they become sufficiently activated in situ by locally released or displayed cytokines and chemoattractants for integrin-mediated firm adhesion [22].
• These observations led to the hypothesis that sulfatide may play a role in facilitating the disengagement of CD62, allowing the efficient exit of granulocytes from the blood stream at sites of inflammation [23].

Physical interactions of SELP

• In adults, after in vitro activation of platelets with thrombin and ADP, VWF binding to platelets increased and correlated significantly with CD62P expression (r = 0.71, p < 0.001) [24].
• EMP were analyzed by fluorescent activated cell sorting (FACS), detecting the particels via expression of CD62 (E-selectin) and anionic phospholipids binding to annexin V [25].

Regulatory relationships of SELP

• In wheals of > or = 6 h duration, GMP-140 was only weakly expressed whereas ELAM-1 and ICAM-1 were markedly up-regulated in lesional and less so in nonlesional skin of acute, chronic recurrent and delayed pressure urticaria [26].
• GPVI-deficient platelets showed some fibrinogen binding in response to collagen but failed to aggregate and to express CD62 and CD63 [27].
• In vitro studies of anticoagulated whole blood inoculated with Neisseria meningitidis supported these clinical findings with marked increases in PMNL CD11b/CD18 expression and activation but no detectable changes in platelet-activated alphaIIbbeta3 or CD62P expression [28].
• However, Serratia treatment almost completely abolished the increase in platelet surface GMP-140 induced by low concentrations of alpha-thrombin (0.5 nmol/L) and diminished the downregulation of platelet surface GPIX by 60.9% +/- 5.6% (mean +/- SEM, n = 3) [29].
• To detect only the activated form of PMPs, a new ELISA needs to be developed, and it will likely use a combination of antibodies that detect platelet activation markers such as P-selectin (CD62P) or activated GPIIb/IIIa [30].

Other interactions of SELP

• In endothelial cells treated with secretagogues that stimulate vWf release the elongated structures positive for PADGEM disappeared, further identifying these structures as Weibel-Palade bodies [18].
• Platelet activation was characterized by flow cytometric measurement of GPIIb/IIIa and GMP-140 in whole blood and washed platelets suspensions, with antihuman fluorescent monoclonal antibodies [31].
• The estimation of platelet adhesion and activation was performed with two enzyme immunoassays (EIAs) using monoclonal antibodies directed against CD42b (GP lb) and CD 62 (GMP 140 or P-Selectin) [32].
• Agreeing with previous data, less than 2% of platelets from peripheral blood of normal individuals expressed the activation markers CD62P or CD63 [33].
• Platelet GMP-140, along with ELAM-1 and gp90MEL, comprise the LEC-CAM family of cell-cell adhesion proteins [34].

Analytical, diagnostic and therapeutic context of SELP

• Immunofluorescence staining of permeabilized human umbilical vein endothelial cells with KC4, a well characterized monoclonal antibody to PADGEM, showed positively stained elongated structures similar in distribution and shape to Weibel-Palade bodies [18].
• Some capillary EC around thyroid follicles (perifollicular EC) were strongly positive for GMP-140 in the Graves' thyroids in contrast to a negative staining on the same structures in the control glands [4].
• Circulation of through the perfusion system resulted in platelet activated as demonstrated by the increased percentage of platelets positive for antigens CD62P and CD63 [35].
• The expression of ELAM-1, GMP-140, carbohydrate structures and lectins in gingival specimens was also studied by immunohistochemistry [36].
• There was no significant difference in GMP-140 levels between TTP/HUS patients with good and poor prognoses; this may be owing to the release of GMP-140 from platelets [37].

References