Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Selectins”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 253 records · Page 14Linked to original sources
PubMed1996

Infectious susceptibility and severe deficiency of leukocyte rolling and recruitment in E-selectin and P-selectin double mutant mice.

During the initial phase of the inflammatory response, leukocytes marginate and roll along the endothelial surface, a process mediated largely by the selectins and their ligands. Mice with mutations in individual selectins show no spontaneous disease and have mild or negligible deficiencies of inflammatory responses. In contrast, we find that mice with null mutations in both endothelial selectins (P and E) develop a phenotype of leukocyte adhesion deficiency characterized by mucocutaneous infections, plasma cell proliferation, hypergammaglobulinemia, severe deficiencies of leukocyte rolling in cremaster venules with or without addition of TNF-alpha, and an absence of neutrophil emigration at 4 h in response to intraperitoneal Streptococcus pneumoniae peritonitis. These mice provide strong evidence for the functional importance of selectins in vivo.

Animals↗
PubMed2007

Generation of soluble P- and E-selectins in vivo is dependent on expression of P-selectin glycoprotein ligand-1.

BACKGROUND: Factors contributing to the generation of soluble P- and E-selectins remain unclear. RESULTS: This work demonstrates that mice lacking P-selectin glycoprotein ligand-1 (Psgl-1(-/-)) are deficient in soluble P-selectin (sP-sel), which is due to a defective binding interaction between PSGL-1 and P-sel, because mice lacking alpha(1,3)-fucosyltransferase-VII are also deficient in sP-sel. Psgl-1(-/-) mice are also deficient in soluble E-selectin (sE-sel) indicating that leukocyte interactions with endothelial cells lead to the generation of sE-sel. The generation of sE-sel requires an interaction between PSGL-1 and P-sel, as deficiency of sE-sel is observed in both Psgl-1(-/-) and P-sel(-/-) mice. Bone marrow transplantation from Psgl-1(-/-) to Psgl-1(+/+) mice leads to deficiency of sP-sel and sE-sel in recipient mice, establishing the importance of bone marrow-derived PSGL-1 toward the generation of sP-sel and sE-sel. Bone marrow transplantation from P-sel(-/-) to P-sel1(+/+) mice does not lead to a significant reduction in sP-sel, confirming the importance of the endothelium toward the liberation of sP-sel. CONCLUSION: sP-sel and sE-sel reflect an interaction between leukocyte PSGL-1 and endothelial P-sel.

Animals↗
PubMed1997

Leukocyte adhesion in angiogenic blood vessels. Role of E-selectin, P-selectin, and beta2 integrin in lymphotoxin-mediated leukocyte recruitment in tumor microvessels.

Interaction of circulating leukocytes with tumor microvasculature is a critical event in the recruitment of effector cells into the tumor stroma. We have examined the ability of lymphotoxin (TNF-beta), to stimulate rolling, adhesion, and transmigration of leukocytes in angiogenic blood vessels induced by tumor spheroids of Lewis lung carcinoma (LLC) implanted in dorsal skinfold chambers of nude mice. In the absence of cytokine stimulation, circulating leukocytes failed to appreciably interact with tumor microvessels (TMV), although significant rolling and adhesion was observed in normal vessels. However, stimulation with lymphotoxin (LT) resulted in a rapid increase in the number of fast and slow rolling leukocytes in TMV. Treatment with anti-P-selectin mAb 5H1 resulted in inhibition of fast rollers alone, while combination treatment with anti-P-selectin and anti-E-selectin (9A9) mAbs effectively blocked slow rolling of leukocytes. Superfusion of the lymphotoxin-stimulated neovasculature with leukotriene B4 (LTB4) resulted in stable cell adhesion followed by emigration of leukocytes into the tumor stroma. LTB4-mediated adhesion and transmigration was significantly inhibited by treatment with anti-beta2 mAb 2E6. These studies delineate a multistep cascade of leukocyte adhesion in TMV and demonstrate that stimulation of the neovasculature with cytokines and chemoattractants can result in P- and E-selectin-dependent rolling and beta2-dependent stable adhesion followed by transmigration into the tumor stroma.

Animals↗
PubMed1994

Attenuation of oxidant-induced lung injury by 21-aminosteroids (lazaroids): correlation with the mRNA expression for E-selectin, P-selectin, ICAM-1, and VCAM-1.

We compared the effects of treatment with methylprednisolone or the 21-aminosteroids, U-74389 and U-74006F (Tirilizad mesylate), on hyperoxic lung injury and the associated expression of mRNA for several adhesion molecules in rats. Inhalation of > 95% oxygen for up to 72 hr in Sprague-Dawley rats produced a marked increase in lung weight and an accumulation of fluid in the thorax when compared with air-breathing controls. Hyperoxia also induced a marked neutrophil-rich influx of inflammatory cells into the bronchial lumen as measured by bronchoalveolar lavage. Neutrophil numbers in bronchoalveolar lavage fluid peaked after 60 hr of exposure to s 95% oxygen; this was associated with a marked upregulation of mRNA for the adhesion molecules P-selectin and E-selectin but not VCAM-1. mRNA for ICAM-1 was constitutively expressed at high levels in both air-breathing controls and in the lungs of rats exposed to high concentrations of oxygen. Pretreatment with the 21-aminosteroids reduced hyperoxic lung damage and improved survival times in animals exposed to > 95% oxygen. However, treatment with methylprednisolone significantly decreased survival times. Treatment with U-74389 did not significantly (p > 0.05) inhibit the BAL neutrophilia and did not significantly (p > 0.05) reduce hyperoxia-induced increases in mRNA expression for P-selectin and E-selectin. The inhibition of hyperoxic lung damage coupled with improved survival seen in treated animals suggests that 21-aminosteroids may provide valuable treatments for pulmonary disorders in which oxidant damage has been implicated.

Animals↗
PubMed1999

A circulating bovine gamma delta T cell subset, which is found in large numbers in the spleen, accumulates inefficiently in an artificial site of inflammation: correlation with lack of expression of E-selectin ligands and L-selectin.

Tissue-specific localization of TCR-defined subsets of gamma delta T cells has been widely reported; however, the mechanisms responsible for this phenomenon are poorly understood. We describe a bovine gamma delta T cell TCR-associated subset that preferentially localizes in the spleen. This subset was characterized by coexpression of CD8, and was found to lack surface expression of E-selectin ligands, GR Ag ligands, as well as low expression of L-selectin. The CD8-positive gamma delta T cell subset did not accumulate at sites of inflammation as efficiently as CD8-negative gamma delta T cells that, in contrast, express E-selectin and GR ligands and high levels of L-selectin. This is the first demonstration of a gamma delta T cell subset, which exhibits a defined tissue tropism, having a unique adhesion molecule expression profile. These results demonstrate that in some cases tissue-specific accumulation of gamma delta T cell subsets can be predicted by expression, or lack of expression, of defined homing molecules.

Animals↗
PubMed2001

Increasing plasma levels of soluble cell adhesion molecules (sE-Selectin, sP-Selectin and sICAM-1) in overweight adults with combined hyperlipidemia.

Combined hyperlipidemia (coincident present hypercholesterolemia and hypertriglyceridemia) may contribute to the development of atherosclerosis and coronary artery disease by increasing of cell adhesion molecules (CAMs). Although the cellular expression of CAMs is difficult to assess clinically, soluble forms of CAMs (sCAMs) are present in the circulation and may serve as marker of CAMs. The aim of this study was to determine whether combined hyperlipidemia in overweight adults without clinical evidence of cardiovascular disease, diabetes mellitus or hypertension is associated with increased expression of CAMs. We examined the levels of soluble cell adhesion molecules (sICAM-1, sE-Selectin and sP-Selectin) in blood plasma of overweight adults (n = 36), mean of BMI 27.08 +/- 4.12 kg/m2 with combined hyperlipidemia, with total cholesterol (TC) 7.27 +/- 1.50 mmol/l, LDL cholesterol 4.89 +/- 1.35 mmol/l, HDL cholesterol 1.27 +/- 0.51 mmol/l and triglycerides (TG) 4.08 +/- 2.22 mmol/l before lipid-lowering therapies, and in equal numbers of age, sex and BMI matched controls. Patients with combined hyperlipidemia had significantly higher plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1) (298.13 +/- 41.24 ng/ml versus 241.35 +/- 37.48 ng/ml; P < 0.001), sE-Selectin (63.31 +/- 9.48 ng/ml versus 42.16 +/- 14.18 ng/ml; P < 0.001) and sP-Selectin (161.18 +/- 20.85 ng/ml versus 111.54 +/- 26.12 ng/ml; P < 0.001) compared with overweight, non-hyperlipidemic control subjects. Combined hyperlipidemia in adults with overweight is associated with elevated soluble plasma levels of CAMs. We suppose that levels of CAMs in these patients may be determined as a marker for appreciation of their potential atherosclerotic burden.

Arteriosclerosis↗
PubMed1998

The Fcgamma receptor-mediated respiratory burst of rolling neutrophils to cytokine-activated, immune complex-bearing endothelial cells depends on L-selectin but not on E-selectin.

Intracellular H2O2 generation, as a measure of the respiratory burst, was determined after stimulation of neutrophils by immune complex (IC)-bearing human umbilical vein endothelial cells. Under static conditions, neutrophils basically responded to the immune deposits on resting endothelial cells. The rotating shear forces of approximately 0.7 dynes/cm2, corresponding to the physiological flow in postcapillary venules, completely abolished this basal H2O2 generation. After activation of the IC-bearing endothelial layers with interleukin-1 (IL-1) or tumor necrosis factor (TNF), or both, for 4 hours, rolling adhesion of the neutrophils was induced, accompanied by considerable H2O2 production. The neutrophil respiratory burst was prominently inhibited by anti-FcgammaRIII MoAb 3G8 (72.4%), and partially by MoAb 2E1 against FcgammaRII (38.5%). Both MoAbs together inhibited the Fc-mediated H2O2 generation by 93. 4%. The respiratory burst and rolling adhesion were markedly blocked by MoAb LAM1-3 against L-selectin (91.3%), whereas the nonfunctional anti-L-selectin MoAb LAM1-14 was ineffective. F(ab)2' fragments of MoAb 7A9 against E-selectin inhibited neutrophil rolling by 98.6%, but not the respiratory burst. Moreover, rolling adhesion of neutrophils and the related oxidative burst were CD11b/CD18- independent. In summary, L-selectin has a unique auxiliary function in triggering the FcgammaR-mediated respiratory burst of rolling neutrophils to IC-bearing endothelial cells, thereby substituting CD11b/CD18 under conditions of flow.

Antigen-Antibody Complex↗
PubMed1996

E-selectin binding promotes neutrophil activation in vivo in E-selectin transgenic mice.

E-selectin is a membrane protein expressed by endothelial cells activated by cytokines released during the inflammatory process; it plays an important role in neutrophil emigration into inflamed tissues. To further explore in vivo the function of E-selectin, we have generated transgenic mouse line expressing E-selectin under the control of a chicken beta-actin promoter. In these mice, the number of blood neutrophils was reduced, without any other obvious phenotype or tissue damage. These neutrophils, however, displayed two significant changes: first, an alteration in the levels of expression of two membrane receptors involved in neutrophil adhesion to endothelial cells, namely a marked increased in the Mac-1 antigen (CD11b/CD18) and a decrease in the Mel-14 antigen (L-selectin); second, an increased oxidative activity when compared to blood neutrophils of non-transgenic mice, as shown by their capacity to oxidize 2',7'-dichlorofluorescein (DCFH) into a fluorescent compound. These observations indicate that the binding of E-selection with neutrophils bearing its ligands promotes neutrophil activation in vivo.

Actins↗
PubMed1994

Effect of inhibiting leukocyte integrin (CD18) and selectin (L-selectin) on susceptibility to infection with Pseudomonas aeruginosa.

Leukocyte (WBC) adherence to endothelial cells has been implicated in the pathogenesis of microvascular injury. The process of leukocyte adherence is mediated by both the integrin and selectin families of molecules, and their interaction with specific endothelial ligands. Antibodies directed against the leukocyte integrin CD18 and L-selectin have been developed and functionally inhibit leukocyte adherence in models of inflammatory injury. We asked the question: Does inhibition of leukocyte adherence by administration of monoclonal antibody directed against either CD18, integrins (R15.7, R7.1) or against L-selectin (DREG 200) increase susceptibility to infection? New Zealand white rabbits were shaved and injected subcutaneously on their dorsum with Pseudomonas aeruginosa (ATCC#27853) at two sites each of 10(8) and 10(7) colony forming units. Animals were monitored with daily determination of weight, temperature, WBC counts, hematocrit, and killed at 1 week for determination of abscess formation. There were four blinded experimental groups: (1) Saline (2 mL/kg); (2) DREG 200 (2 mg/kg); (3) R7.1 (2 mg/kg); or (4) R15.7 (2 mg/kg). At the 10(7) and 10(8) injection sites the R15.7 group had an increased rate and size of abscess formation compared with controls. The R7.1 group had an increased rate at the 10(8) injection site. There was no significant difference in the percentage of the abscess formation or mean area between the controls and DREG 200-treated groups. We conclude that giving antibody to CD18 increased susceptibility to infection while giving antibody to L-selectin does not.

Animals↗
PubMed2005

[Expression of L-selectin on the surface of neutrophils stimulated by TNF-alpha and level of sL-selectin in serum of patients with lung cancer].

The aim of the study was to estimate L-selectin expression on peripheral blood PMN stimulated by TNF-alpha and concentration of a soluble form of L-selectin in serum of patients with small cell and non-small cell lung cancer. The results showed an increased expression of L-selectin on PMN isolated from peripheral blood and an elevated concentration of sL-selectin in serum of patients with small cell and non-small cell lung cancer. An increased expression of these adhesion molecules may be the result of neutrophil activation by inflammatory cytokines.

Carcinoma, Non-Small-Cell Lung↗
PubMed2000

Expression of VCAM-1, ICAM-1, E-selectin, and P-selectin on endothelium in situ in patients with erythroderma, mycosis fungoides and atopic dermatitis.

BACKGROUND: Erythroderma may result from different causes. At present it is unclear whether the patho-mechanisms that lead to these different types of erythroderma are identical or different. Adhesion molecules and their ligands play a major role in endothelial-leukocyte interactions, which affect the binding, transmigration and infiltration of lymphocytes and mononuclear cells during inflammation, injury, or immunological stimulation. The aim of this study was to investigate the adhesion molecule expression on endothelial cells in erythroderma in situ. METHODS: Snap-frozen skin biopsy specimens from 23 patients with erythroderma were studied. Eight had idiopathic erythroderma, 5 erythrodermic atopic dermatitis, 4 Sézary syndrome and 6 had erythroderma from miscellaneous causes. As a control we studied skin specimens from 10 patients with mycosis fungoides, 5 patients with atopic dermatitis and 5 healthy non-atopic volunteers. To determine adhesion molecule expression on endothelial cells in situ, sections were immuno-histochemically double stained with biotinylated Ulex Europaeus agglutinin 1 as a pan-endothelial cell marker, and for the adhesion molecules VCAM-1, ICAM-1, E-, and P-selectin. All double- and single-stained blood vessels in the dermis were counted. RESULTS: Mean endothelial expression in erythroderma was as follows: VCAM-1 51.4%, ICAM-1 70.1%, E-selectin 43.5%, and P-selectin 52.6%. There was no statistical difference between different groups of erythroderma. Mean expression of all adhesion molecules tested, was in Sézary syndrome higher than in mycosis fungoides albeit not significant. In erythrodermic atopic dermatitis only VCAM-1 expression was significantly higher than in lesional skin of atopic dermatitis. No differences were observed in expression of the other three adhesion molecules. CONCLUSIONS: There is no difference regarding adhesion molecule expression on endothelial cells between different types of erythroderma.

Cell Adhesion Molecules↗
PubMed2001

Increased levels of soluble adhesion molecules, E-selectin and P-selectin, in patients with infective endocarditis and embolic events.

AIMS: Inflammation-induced procoagulant changes and endothelial cell activation appear to play an important role in thromboembolic complications of infective endocarditis. Hence, the aim of this study was to compare the plasma levels of soluble adhesion molecules E- and P-selectin in infective endocarditis patients with and without embolic events, and healthy subjects. METHODS AND RESULTS: The study group consisted of 76 consecutive patients (mean age=26 years old, range from 8 to 64 years) with definite infective endocarditis according to the Duke criteria. Thirteen of the patients (17.1%) had embolic events. Transoesophageal echocardiographic examinations were performed on all patients within 3 days of initiation of antimicrobial therapy. Although there was a trend towards a higher rate of vegetations detected in those with embolic events than in those without, this did not reach statistical significance (84.6% vs 80.9%, P>0.05). Significantly larger vegetations were observed in patients with embolic events as compared to those without embolic events (1.4 cm vs 1.0 cm, P=0.03). The mean plasma concentrations of P-selectin were elevated in patients with embolic events as compared to both patients without embolic events and control subjects (58.69+/-7.49 ng x ml(-1)vs 29.65+/-5.69 ng x ml(-1), P=<0.001 and 58.69+/- 7.49 ng x ml(-1) vs 25.82+/-5.38 ng x ml(-1), P<0.001). Similarly, the patients with embolic events had increased plasma levels of E-selectin compared to those without embolic events and the control group (73.15+/-11.47 ng x ml(-1) vs 42.84+/-8.77 ng x ml(-1), P<0.001 and 73.15+/- 11.47 ng x ml(-1) vs 34.23+/-5.92 ng x ml(-1), P<0.001). CONCLUSION: Determination of these membrane activation molecules may provide useful markers with which to identify patients at high thromboembolic risk from infective endocarditis.

Adolescent↗
PubMed1996

Effects of E-selectin and P-selectin blockade on neutrophil sequestration in tissues and neutrophil oxidative burst in burned rats.

OBJECTIVE: Neutrophil deposition in tissues (leukosequestration) after shock may produce local tissue injury from proteases and high-energy oxygen species released from sequestered neutrophils. The initial step in the binding of neutrophils to capillary endothelium is the interaction of adhesion molecule (selectin) receptors between neutrophils and endothelial cells. We quantified leukosequestration in the tissues of burned rats using two methods of analysis: a) measurement of lung myeloperoxidase; and b) measurement of radiolabeled neutrophils and erythrocytes deposited in multiple tissues. We then determined the ability of a selectin receptor blocking agent to affect neutrophil deposition in tissues after burn injury. DESIGN: Prospective, controlled, laboratory study. SETTING: University research laboratory. SUBJECTS: Male Wistar rats (200 to 300 g). INTERVENTIONS: After tracheostomy and venous cannulation, rats received 17% total body surface area full-thickness contact burns and were resuscitated with saline (20 mL i.p.). Experimental animals received 2 mg/kg body weight i.v. administration of a P- and E-selectin blocking monoclonal antibody, CY-1747, immediately after burn. Lung tissue neutrophils were estimated by measuring myeloperoxidase in lung tissue. Neutrophil retention in lung, liver, spleen, gut, skin, muscle, kidney, and brain tissues was determined by removing (preburn) and differentially radiolabeling neutrophils (111In) and erythrocytes (51Cr), reinfusing cells 4.5 hrs after burn, and measuring tissue radioactivity 30 mins later. Edema was estimated by measuring extravasated 125 I-labeled albumin in the various tissues. Peripheral blood neutrophils were analyzed for intracellular hydrogen peroxide content, utilizing a fluorescent dye that reacts with hydrogen peroxide, coupled with analysis of cell fluorescence by flow cytometry. MEASUREMENTS AND MAIN RESULTS: Myeloperoxidase concentration was increased in lungs 5 hrs after burn (p < .05), indicating neutrophil deposition. Radioisotope studies demonstrated significant (p < .05) leukosequestration into the lung, gut, kidney, skin, and brain tissues at 5 hrs after burn. Flow cytometry showed increased intracellular hydrogen peroxide content in peripheral blood neutrophils 5 hrs after burn. Tissue edema, manifested by radiolabeled albumin retention, was not seen in any tissues. Postburn neutrophil deposition in lungs and liver was blocked (p < .05) by administration of CY-1747 after burn, but maximal neutrophil hydrogen peroxide content was unaffected. CONCLUSION: Burn injury in rats results in accumulation of neutrophils in multiple tissues. Neutrophil deposition in the lungs and liver is blocked by administration of the E/P-selectin blocking antibody, CY-1747. Since sequestration of metabolically active neutrophils may induce tissue injury, therapies that block postburn leukosequestration may improve clinical outcomes by limiting remote tissue injury.

Animals↗
PubMed2000

Serum L-selectin and P-selectin levels in lymphomas.

The migration of normal and malignant lymphoid cells is governed by specific adhesion molecules. Selectins comprise a family of adhesion receptors expressed by leukocytes, platelets and endothelial cells. In this study, the serum levels of soluble L-selectin and P-selectin were measured in patients with non-Hodgkin's lymphoma and Hodgkin's disease and found to be significantly elevated in both patient groups compared to healthy controls. This result provides evidence that alterations in the expression and function of adhesion molecules may play an important role in the progression of lymphomas. Further studies are awaited to establish the exact roles of these adhesion molecules in distinct patterns of growth and spread of lymphomas.

Adult↗
PubMed1995

The selectins: insights into selectin-induced intracellular signaling in leukocytes.

Characteristic features of the inflammatory and immune responses involve the recruitment of leukocytes to sites of tissue injury and the recirculation of lymphocytes through hematopoietic and lymphoid tissues. Recent studies indicate that the regulated cell surface expression of a family of protein adhesion molecules known as selectins and their counterreceptors on both leukocytes and endothelium play critical roles in both biologic processes. Initially, the function of these molecules was thought to be restricted to regulating cell-cell adhesive interactions. Selectin-dependent cell-cell binding has been shown to be essential in localizing leukocytes within tissues by promoting cell rolling along endothelium prior to the development of tight adhesion and subsequent cell migration. However, recent studies suggest that these molecules also play an active role in regulating additional leukocyte functions. This article will review the emerging evidence that indicates a broader and significant role of selectin molecules and their counterreceptors in the initiation of intracellular signaling pathways and regulation of other leukocyte functional responses including degranulation, cytokine expression, activation of the respiratory burst, and T lymphocyte activation.

Animals↗
PubMed2005

Quinic acid derivatives as sialyl Lewis(x)-mimicking selectin inhibitors: design, synthesis, and crystal structure in complex with E-selectin.

A search for noncarbohydrate sLe(x) mimics led to the development of quinic acid derivatives as selectin inhibitors. At Wyeth we solved the first cocrystal structure of a small molecule, quinic acid, with E-selectin. In the cocomplex two hydroxyls of quinic acid mimic the calcium-bound fucose of the tetrasaccharide sLe(x). The X-ray structure, together with structure based computational methods, was used to design quinic acid based libraries that were synthesized and evaluated for their ability to block the interaction of sLex with P-selectin. A large number of analogues were prepared using solution-phase parallel synthesis. Selected compounds showed decrease in leukocyte rolling in the IVM mouse model. Compound 2 inhibited neutrophil influx in the murine TIP model and demonstrated good plasma exposure.

Animals↗
PubMed2002

P-selectin glycoprotein ligand-1 (rPSGL-Ig)-mediated blockade of CD62 selectin molecules protects rat steatotic liver grafts from ischemia/reperfusion injury.

We examined the effects of early blockade of CD62 selectin-mediated adhesive interactions in steatotic rat liver models of ex vivo cold ischemia followed by reperfusion or transplantation by administration of P-selectin glycoprotein ligand-1 (rPSGL-Ig). In the model of cold ischemia/reperfusion, livers pretreated ex vivo with rPSGL-Ig at harvesting from obese Zucker rats showed significantly decreased portal resistance, increased bile production, and diminished hepatic endothelial neutrophil infiltration, as compared with untreated controls. Pretreatment of fatty livers with rPSGL-Ig prior to transplantation extended the survival of lean Zucker rat recipients from 40% to 90%. This effect correlated with significantly improved liver function, depressed neutrophil activity, and decreased histologic features of hepatocyte injury. Intragraft expression of CD62 P-selectin was similar in both recipient groups. rPSGL-Ig treatment decreased intragraft infiltration by CD3/CD25 cells, diminished expression of pro-inflammatory TNFalpha, IL-6, iNOS, IL-2 and IFN-gamma, without significantly affecting mRNA levels coding for anti-inflammatory IL-4. Thus, rPSGL-Ig blockade of CD62-mediated adhesive interactions protects against severe ischemia/reperfusion injury suffered otherwise by steatotic rat livers. These findings document the potential utility of rPSGL-Ig in increasing the transplant donor pool through modulation of marginal steatotic livers.

Animals↗
PubMed2000

Modification of P-selectin glycoprotein ligand-1 with a natural killer cell-restricted sulfated lactosamine creates an alternate ligand for L-selectin.

Natural killer (NK) cells are components of the innate immune system that can recognize and kill virally infected cells, tumor cells, and allogeneic cells without prior sensitization. NK cells also elaborate cytokines (e.g., interferon-gamma and tumor necrosis factor-alpha) and chemokines (e.g., macrophage inflammatory protein-1alpha) that promote the acquisition of antigen-specific immunity. NK cell differentiation is accompanied by the cell surface expression of a mucin-like glycoprotein bearing an NK cell-restricted keratan sulfate-related lactosamine carbohydrate, the PEN5 epitope. Here, we report that PEN5 is a post-translational modification of P-selectin glycoprotein ligand-1 (PSGL-1). The PEN5 epitope creates on PSGL-1 a unique binding site for L-selectin, which is independent of PSGL-1 tyrosine sulfation. On the surface of NK cells, the expression of PEN5 is coordinated with the disappearance of L-selectin and the up-regulation of Killer cell Ig-like Receptors (KIR). These results indicate that NK cell differentiation is accompanied by the acquisition of a unique carbohydrate, PEN5, that can serve as part of a combination code to deliver KIR(+) NK cells to specific tissues.

Amino Sugars↗