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 703 records · Page 39Linked to original sources
PubMed2005

Soluble P-selectin concentration in patients with colorectal cancer.

During platelet activation, P-selectin is translocated onto the external platelet membrane. Surface exposure of P-selectin is temporary, and the molecule undergoes endocytosis or shedding to the circulation where it appears in a soluble form as sP-selectin. The aim of the study was to assess platelet activation based on the level of soluble form of P-selectin (sP-selectin) in colorectal cancer patients. The study involved 22 surgically treated patients, divided into two groups depending on histopathological malignancy grade: group I - patients with low malignancy grade (G2), group II - patients with high malignancy grade (G3). The examinations were carried out three times: before surgery (A0) and 3 (A1) and 12 days (A2) after the surgery. Control group (C) consisted of 20 healthy subjects. The sP-selectin level was determined in the plasma using the ELISA Kit (Human sP-selectin, R&D System). In colorectal cancer patients sP-selectin concentration was statistically significantly higher (69.25 ng/ml in group I and 66.50 ng/ml in group II) as compared to healthy subjects (46.01 ng/ml) (p<0.05), irrespective of malignancy grade. The surgical procedure has a significant effect on the dynamics of changes in the level of sP-selectin. Initially, 3 days (A1) after the procedure, there is a decrease in the level of sP-selectin, but after 12 days (A2) a rise is noted again, the level being the highest in group I. It indicates that the surgical procedure does not totally eliminate the factors responsible for platelet activation and did not normalize platelet activation.

Adenocarcinoma↗
PubMed2006

[Expression of transforming growth factor-beta 1, vascular cell adhesion molecule-1 and endothelium-selectin in placenta of patients with pre-eclampsia].

OBJECTIVE: To study the change and significance of the expression of transforming growth factor-beta 1 (TGF-beta1), vascular cell adhesion molecule-1 (VCAM-1) and endothelium-selectin (E-selectin) in placenta of patients with pre-eclampsia. METHODS: Twenty normal pregnant women (control group) and 40 women with pre-eclampsia (pre-eclampsia group, including 16 women with mild pre-eclampsia and 24 women with severe pre-eclampsia) were selected. The cellular distribution of TGF-beta1, VCAM-1 and E-selectin in placenta in both groups was determined by immunohistochemistry, and the mean density was measured by computer image analysis system. RESULTS: (1) The level of TGF-beta1 in placental villous syncytiotrophoblast of pre-eclampsia group (70.7 +/- 0.5) was significantly higher than that of control group (70.3 +/- 0.6), while the level of VCAM-1 and E-selectin in pre-eclampsia group (VCAM-1: 82.5 +/- 0.5, E-selectin: 53.5 +/- 0.5) was significantly lower than that of control group (VCAM-1: 82.8 +/- 0.3, E-selectin: 53.8 +/- 0.4) (P < 0.05). However, there were no significant differences in women with mild pre-eclampsia (TGF-beta1: 70.6 +/- 0.6, VCAM-1: 82.4 +/- 0.6, E-selectin: 53.4 +/- 0.5) and severe ones (TGF-beta1: 70.8 +/- 0.4, VCAM-1: 82.6 +/- 0.5, E-selectin: 53.6 +/- 0.5) (P > 0.05); (2) The level of E-selectin in placental villous capillary endothelial cells of pre-eclampsia group (63.0 +/- 0.5) was significantly higher than that of control group (62.6 +/- 0.4) (P < 0.05), while there was no significant difference in women with mild pre-eclampsia (63.2 +/- 0.4) and severe pre-eclampsia (62.9 +/- 0.5) (P > 0.05). CONCLUSION: TGF-beta1, VCAM-1 and E-selectin are not only related to placenta shallow bed of pre-eclampsia, but also participate in pathogenic process of vascular endothelial damage of pre-eclampsia.

Adult↗
PubMed1994

Down-regulation of L-selectin surface expression by various leukocyte isolation procedures.

L-selectin, a cell surface glycoprotein expressed on lymphocytes, granulocytes, and monocytes, has been implicated in lymphocyte homing and extravasation of phagocytic leukocytes into areas of inflammation. Considerable differences of L-selectin expression among various individuals has been reported, with clinical correlations to perinatal events, maturation, and circadian rhythm. In this study, L-selectin expression of various white blood cells was found to be differentially sensitive to ficoll-hypaque or percoll density gradient centrifugation. After density gradient centrifugation, a significant loss of median monocyte L-selectin expression was observed when compared to time and temperature-matched controls or results obtained by whole blood incubation with anti-L-selectin monoclonal antibodies followed by simultaneous leukocyte fixation and red cell lysis. Mock treatment itself was associated with a variable L-selectin loss of monocytes but not lymphocytes or granulocytes. Ficoll-hypaque or percoll density gradient centrifugation resulted in significant L-selectin down-regulation of lymphocytes while granulocytes separated from lymphocytes and monocytes by ficoll-hypaque or percoll retained full L-selectin surface reactivity. L-selectin downregulation was seen also after colloid sedimentation with hydroxy-ethyl starch. It is concluded that unseparated blood should be used for measuring L-selectin expression.

Cell Adhesion↗
PubMed1994

Down-regulation of L-selectin surface expression by various leukocyte isolation procedures.

L-selectin, a cell surface glycoprotein expressed on lymphocytes, granulocytes, and monocytes, has been implicated in lymphocyte homing and extravasation of phagocytic leukocytes into areas of inflammation. Considerable differences of L-selectin expression among various individuals has been reported, with clinical correlations to perinatal events, maturation, and circadian rhythm. In this study, L-selectin expression of various white blood cells was found to be differentially sensitive to ficoll-hypaque or percoll density gradient centrifugation. After density gradient centrifugation, a significant loss of median monocyte L-selectin expression was observed when compared to time and temperature-matched controls or results obtained by whole blood incubation with anti-L-selectin monoclonal antibodies followed by simultaneous leukocyte fixation and red cell lysis. Mock treatment itself was associated with a variable L-selectin loss of monocytes but not lymphocytes or granulocytes. Ficoll-hypaque or percoll density gradient centrifugation resulted in significant L-selectin down-regulation of lymphocytes while granulocytes separated from lymphocytes and monocytes by ficoll-hypaque or percoll retained full L-selectin surface reactivity. L-selectin downregulation was seen also after colloid sedimentation with hydroxy-ethyl starch. It is concluded that unseparated blood should be used for measuring L-selectin expression.

Cell Adhesion Molecules↗
PubMed1995

Primitive human hematopoietic progenitors adhere to P-selectin (CD62P).

P-selectin was shown to bind committed human hematopoietic progenitors (colony-forming unit-granulocyte-macrophage [CFU-GM] and burst-forming unit-erythroid [BFU-E]) as identified by their expression of the CD34 antigen and by in vitro clonogenic assays. In addition, P-selectin bound all precursors (pre-CFU) of committed myeloid progenitors assayed by their ability to sustain hematopoiesis in both conventional stroma-containing and stroma-free, cytokine-dependent systems. Binding of CD34+ cells to P-selectin was temperature-independent and shear-resistant, occurred only in the presence of divalent cations, was protease sensitive, and was completely blocked by anti-P-selectin antibody. Neuraminidase treatment of CD34+ cells completely abrogated their binding to P-selectin, implying a prominent role for sialic acid in the structure and function of the P-selectin ligand on hematopoietic progenitors. Monoclonal antibodies (MoAbs) CSLEX-1 and HECA-452, which identify carbohydrate epitopes involving sialic acid, bound to 33% and 35% of CD34+ cells, respectively, and included the majority of CFU-GM and pre-CFU. Three-color flow cytometric analysis showed a precise codistribution of CSLEX-1 and HECA-452 antigens on CD34+ cells, implying recognition of the same glycoprotein antigen by the two MoAbs. Treatment of CD34+ cells with neuraminidase completely abolished binding of both MoAbs. In addition, HECA-452 partially blocked the adhesion of CD34+ cells to P-selectin. P-selectin glycoprotein ligand (PSGL-1), recently molecularly cloned from the promyelocytic leukemia cell line HL60, was expressed by CD34+ cells as determined by reverse transcription polymerase chain reaction. Combined with the functional and biochemical characteristics, these data suggest that PSGL-1 may comprise an important P-selectin ligand expressed by primitive hematopoietic cells, but do not preclude the existence of additional P-selectin ligands on these cells.

Antigens, CD↗
PubMed1995

P-selectin regulates platelet-activating factor synthesis and phagocytosis by monocytes.

Adhesion molecules on endothelial cells or platelets may regulate localization and activation of leukocytes at sites of tissue injury, infection, or thrombosis. In these studies, we found that human peripheral blood monocytes adhered specifically to immobilized P-selectin (CD62P), Chinese hamster ovary cells transfected with a cDNA for P-selectin, or endothelial cells stimulated to express P-selectin on the cell surface. P-selectin did not directly stimulate synthesis of the lipid autoacoid platelet-activating factor (PAF); however, incubation on immobilized P-selectin primed monocytes for increased synthesis of PAF in response to opsonized zymosan particles. P-selectin did not stimulate increased surface expression of integrin CD11b/CD18 and did not enhance binding of iC3b-coated erythrocytes, a CD11b/CD18-mediated functional response. P-selectin increased PAF production by monocytes incubated with unopsonized zymosan particles that stimulate this response by interaction with the beta-glucan receptor. Further, phagocytosis of unopsonized zymosan particles, another response triggered by the beta-glucan receptor, was increased following the adherence of monocytes to P-selectin. These data suggested that P-selectin primed monocytes for increased PAF synthesis through regulation of the beta-glucan receptor or regulation of signal transduction mechanisms that are linked to the receptor. P-selectin expressed on endothelial cells or platelets may serve both to localize monocytes at sites of vascular inflammation or thrombosis and to prime the cells for subsequent responses that augment inflammation.

Animals↗
PubMed1995

sLex is not responsible for the interaction of sLex-positive memory T lymphocytes with E-selectin.

E-selectin in an adhesion molecule that is transiently and exclusively expressed on endothelial cells in response to inflammatory cytokines. In addition, E-selectin participates in the initial interaction of leucocytes with activated endothelial cells. This role of E-selectin in cell adhesion has made it a potential target for modulation of inflammatory processes that, for example, are occurring in autoimmune diseases such as rheumatoid arthritis. Although on granulocytes the ligand for E-selectin has been identified as the tetrasaccharide sialyl Lewis x (sLex), the molecular nature of this ligand on T lymphocytes has not yet been identified. In the present study, it was shown by fluorescence-activated cell sorter (FACS) analysis with the anti-sLex antibody CSLEX1 that T lymphocytes stimulated with phytohaemagglutanin (PHA), interleukin-2 (IL-2) and transforming growth factor-beta 1 (TGF-beta 1) expressed sLex. Furthermore, in a cell adhesion assay these activated T cells of the memory phenotype bound specifically to E-selectin-transfected Chinese hamster ovary (E-CHO) cells. This adhesion could be blocked with an anti-E-selectin antibody but not with CSLEX1. In the same assay, the interaction of sLex-positive U937 cells with the E-CHO cells could be inhibited both with anti-E-selectin and CSLEX1 antibodies. From these results it can be inferred that sLex on activated T lymphocytes is not responsible for the interaction with E-selectin. Rather, these results suggest that stimulated T lymphocytes express an additional E-selectin ligand(s) with much higher avidity for E-selectin than sLex.

Animals↗
PubMed1996

Functional and structural characterization of the eosinophil P-selectin ligand.

Our recent studies have indicated an important role for P-selectin in eosinophil adhesion. We have therefore compared eosinophil and neutrophil binding with nasal polyp endothelium as well as purified P-selectin. We have also compared the structure and expression of the eosinophil and neutrophil P-selectin ligands. Using the frozen section assay, eosinophils bound to 2-fold more blood vessels within the nasal polyp tissue than neutrophils. Up to 10-fold more eosinophils than neutrophils bound per unit length of endothelium. Neutrophil and eosinophil binding was inhibited by a mAb against P-selectin and a P-selectin chimera which binds to the P-selectin ligand. Eosinophils bound with approximately 2-fold greater avidity to purified P-selectin under flow conditions. Using SDS-PAGE we characterized the eosinophil P-selectin ligand as a sialylated, homodimeric glycoprotein consistent with the known structure of PSGL-1. However, expression of PSGL-1 by eosinophils was significantly greater than on neutrophils. The eosinophil ligand had a calculated molecular mass by SDS-PAGE of approximately 10 kDa greater than the neutrophil ligand, which was not due to differences in N-glycosylation. Eosinophils expressed the 15-decapeptide repeat form of PSGL-1 compared with neutrophils that have the 16-decapeptide repeat form. The increased binding of eosinophils, compared with neutrophils, to P-selectin in both an ex-vivo and in vitro assay suggests that P-selectin may have a role directing the specific migration of eosinophils in diseases such as asthma. The increased avidity may be due to increased expression of PSGL-1 by eosinophils, differences in the peptide backbone, or post-translational modifications.

Antibodies, Monoclonal↗
PubMed1996

The role of P-selectin and ICAM-1 in acute lung injury as determined using blocking antibodies and mutant mice.

Cobra venom factor (CVF) induces lung injury through oxidant- and neutrophil-dependent mechanisms. Adhesion molecules, particularly L-selectin, P-selectin, CD11/CD18, and ICAM-1, are required for full expression of injury in rats. This study compared the roles of P-selectin and ICAM-1 using either mutant mice or blocking Abs. Mice deficient in either P-selectin, ICAM-1, or both adhesion molecules were compared with wild-type mice. Wild-type and single mutant mice were given Abs against murine P-selectin or ICAM-1. CVF was injected i.v., and neutrophil sequestration and extravascular albumin were measured 30 min later. Neither P-selectin, ICAM-1, nor P-selectin/ICAM-1 double mutants showed a reduction in neutrophil sequestration or lung injury when compared with wild-type mice. Anti-P-selectin Abs inhibited both sequestration and injury in wild-type mice by 57% and 60%, respectively, but had no effect in P-selectin mutants. Similar results were found using anti-ICAM-1 Ab in wild-type mice (78% inhibition of sequestration and 88% inhibition of injury) and ICAM-1 mutant mice (no reduction). These results suggest that the apparent role of these molecules in CVF-induced lung injury depends on the method used to block function. When studied using blocking Abs, both P-selectin and ICAM-1 were required for neutrophil sequestration and lung injury, while neither played a role singly or together when studied using mice with genetic deletions. Abs may inhibit neutrophil sequestration and lung injury through mechanisms other than simply adhesion blockade, or mutant mice may utilize alternative adhesion pathways.

Animals↗
PubMed1996

Soluble P-selectin as parameter for platelet activation during storage.

Platelet concentrates stored at room temperature deteriorate. The so-called storage lesion is characterised by morphological changes and a loss of functionality. To find an assay for early platelet activation in platelet concentrates the morphological score, beta-TG release and P-selectin expression were determined, and compared with the amount of soluble P-selectin. An ELISA was used to quantify soluble P-selectin in the storage medium. We found a significant correlation between the amount of soluble P-selectin and the percentage of P-selectin positive platelets (flow-cytometric analysis) (r = 0.7449; p < 0.0001) or the amount of beta-TG release (r = 0.6837; p < 0.0001). The morphological score also correlated significantly (negative) with the amount of soluble P-selectin (r = -0.7669; p = 0.0002). From day 0 till day 8, the amount of soluble P-selectin increased constantly from 219 +/- 49.2 ng/ml to 556 +/- 102.3 ng/ml. The detection of soluble P-selectin can be used to quantify activation of platelets during storage. The immuno-assay for soluble P-selectin is more sensitive than flow-cytometric analysis of the percentage of P-selectin-positive cells and allows earlier detection of platelet activation.

Biomarkers↗
PubMed1997

Topographic distribution of homing receptors on B and T cells in human gut-associated lymphoid tissue: relation of L-selectin and integrin alpha 4 beta 7 to naive and memory phenotypes.

In mice, integrin alpha 4 beta 7 is the main receptor used by lymphocytes that home to the Peyer's patches, although L-selectin contributes to the initial interaction with high endothelial venules. Less is known about the expression and function of these adhesion molecules in humans. The distribution of L-selectin and alpha 4 beta 7 on various B- and T-cell subsets was examined in human Peyer's patches (n = 8) and appendix (n = 4), collectively called gut-associated lymphoid tissue. Multicolor immunophenotyping was performed on cryosections, and dispersed cells were examined by flow cytometry. In cryosections, CD45RA+ T cells around and within interfollicular high endothelial venules, as well as surface (s)IgD+ B lymphocytes in the follicle mantles, often expressed abundant L-selectin but only intermediate levels of alpha 4 beta 7. CD45RO+ T cells and sIgD- B cells expressed higher levels of alpha 4 beta 7 and were often located near putative efferent lymphatics; only a small fraction (< 20%) of such memory cells expressed L-selectin. By flow cytometry, considerably more T than B lymphocytes co-expressed L-selectin and alpha 4 beta 7 (40% versus 25% and 67% versus 39%, respectively). In samples with many L-selectin+ cells (> 30%), more of these lymphocytes co-expressed alpha 4 beta 7 than in samples with few L-selectin+ cells. Because L-selectin and alpha 4 beta 7 were co-expressed on lymphocytes located near high endothelial venules, and because such co-expression was relatively common when many L-selectin+ cells were present, both of these molecules might participate in homing to human gut-associated lymphoid tissue. Such homing is probably most pronounced for T lymphocytes that were found to express L-selectin and alpha 4 beta 7 more often than B lymphocytes. The selective and relatively high expression of alpha 4 beta 7 on memory cells located near efferent lymphatics indicated a different migratory capacity; after exit from gut-associated lymphoid tissue, such stimulated cells might home mainly to mucosal effector sites.

Adolescent↗
PubMed1997

Role of P-selectin in endotoxin-induced uveitis.

PURPOSE: P-selectin is one of the early-reactive adhesion molecules that play a part in the rolling phase of leukocytes in cellular infiltration. The study objective was to determine whether P-selectin is involved in the development of endotoxin-induced uveitis (EIU). METHODS: Endotoxin-induced uveitis was initiated in male Lewis rats by injecting 200 micrograms lipopolysaccharide (LPS) into the foot pad. Expression of P-selectin in the iris-ciliary body was studied by immunohistochemistry using wholemounts and paraffin embedded sections of iris-ciliary body prepared at various time intervals. A monoclonal antibody (mAb) against P-selectin and a ligand for P-selectin, sialyl Lewis X oligosaccharide (SLeX-OS), was intravenously injected to evaluate the effects of selectin inhibition. The effect of treatment was evaluated by the number of infiltrated cells and protein concentration in the aqueous humor at 24 hours after LPS treatment. RESULTS: P-selectin immunoreactivities were observed in the vessels of the iris in whole iris-ciliary body mounts and on the surface of the microvascular endothelium in paraffin-embedded sections. Activity was most prominent at 15 minutes and at 5 to 7 hours after LPS treatment and was moderate from 1 to 4 hours after treatment. The selective inhibition of P-selectin significantly blocked the cellular infiltration into aqueous humor, but this infiltration was even more effectively inhibited by SLeX-OS. Protein concentration in the aqueous humor was not inhibited by selectin as much as was cellular infiltration. CONCLUSIONS: In the early phase of EIU, P-selectin may be expressed on the vascular endothelium in the iris in a biphasic pattern that modulates the rolling phase of leukocytes. The expression of this molecule may be essential for succeeding processes of cellular infiltration and may determine the subsequent states of ocular inflammation.

Animals↗
PubMed1998

Fever-range hyperthermia enhances L-selectin-dependent adhesion of lymphocytes to vascular endothelium.

The L-selectin leukocyte adhesion molecule plays an important role in controlling leukocyte extravasation in peripheral lymph nodes and at sites of tissue injury or infection. Although febrile responses during infection and inflammation are associated with enhanced immune activity, the contribution of fever-range temperatures to controlling lymphocyte recruitment to tissues has not been previously examined. In this report we provide evidence that direct exposure of lymphocytes to fever-range temperatures (38-41 degrees C) in vitro for 9 to 24 h resulted in a >100% increase in L-selectin-dependent adhesion of these cells to lymph node high endothelial venules (HEV). Moreover, culture of lymphocytes under hyperthermia conditions markedly enhanced the ability of these cells to traffic in an L-selectin-dependent manner to peripheral lymph nodes, mesenteric lymph nodes, and Peyer's patches. In contrast, febrile temperatures did not increase LFA-1 function as assessed by measuring lymphocyte adhesion to ICAM-1-3T3 transfectants. Fever-range hyperthermia further did not increase L-selectin surface density on lymphocytes or L-selectin-dependent recognition of soluble carbohydrate substrates; however, a marked increase in ultrastructural immunogold-labeling of L-selectin was observed in response to thermal stimuli. These results suggest that elevated temperatures enhance L-selectin adhesion and/or avidity through the regulation of L-selectin conformation or organization in the plasma membrane. Finally, the observed thermal effects on L-selectin adhesion were attributed to soluble factors in the conditioned medium of heat-treated cells. Taken together, these data provide new insight into the potential physiologic role of the febrile response in enhancing lymphocyte recruitment to tissues through the regulation of L-selectin adhesion.

Cell Adhesion↗
PubMed1998

Intrinsic differences in L-selectin expression levels affect T and B lymphocyte subset-specific recirculation pathways.

Lymphocyte migration into lymphoid organs is regulated by tissue-specific adhesion molecules such as L-selectin and the alpha4beta7 integrin. Whether L-selectin also regulates lymphocyte subset-specific migration into specific lymphoid tissues was examined in this study by comparing the migration of CD4+ T cells, CD8+ T cells, and B cells from L-selectin-deficient and wild-type mice. T cells were the predominant lymphocyte subset entering PLN, MLN, Peyer's patches, and spleen during short term (1-h) migration assays. However, both B cell and CD4+ and CD8+ T cell entries into PLN, MLN, and Peyer's patches were dramatically impaired (73-98%) by loss of L-selectin. Lymphocyte expression of alpha4beta7 integrin did not compensate for the loss of L-selectin, since both B and T cells predominantly migrated into the spleen in the absence of L-selectin. The more efficient migration of T cells into peripheral lymphoid tissues relative to that of B cells was partly explained by the finding that T cells expressed L-selectin at 50 to 100% higher levels than B cells. In addition, a 50% reduction in L-selectin expression by lymphocytes from hemizygous L-selectin(+/-) mice resulted in a 50 to 70% decrease in short term lymphocyte migration into peripheral lymphoid tissues relative to that of wild-type lymphocytes. Thus, the differential migration of T and B lymphocyte subsets to lymphoid tissues is regulated in part by subset-specific differences in L-selectin expression levels.

Animals↗
PubMed1997

Significance of P-selectin expression in human glomerulonephritis.

OBJECTIVE: To examine the relationship between P-selectin expression and human glomerulonephritis. METHODS: P-selectin expression was investigated in renal biopsies of glomerulonephritis patients (n = 133) by immunohistochemical and in situ hybridization analyses. They were divided into three groups based on the degrees of cells proliferation or sclerosis. Group I: histological lesions in glomeruli are mild (n = 23); Group II: glomerular cells proliferation is prominent (n = 91); Group III: glomerular sclerosis is severe (n = 19). The Kruskal-Wallis test, Chisquare test and Spearman's correlation were used in our study. RESULTS: In normal controls, renal P-selectin expression was negative (n = 10). In glomerulonephritis, the up-regulated P-selectin expression on tubular epithelium was significantly higher than that on glomeruli and interstitium (P < 0.01). P-selectin was expressed predominantly on platelets in glomeruli, and glomerular P-selectin expression was more significantly up-regulated in Group II than in Group I or Group III (P < 0.05; and P < 0.01, respectively). There were strong correlations between the degree of tubulointerstitial lesions and the expression of P-selectin on tubular epithelium or within interstitium (rs = 0.395 and rs = 0.337, P < 0.01). Furthermore, P-selectin messenger RNA (mRNA) signals were also detected in the cytoplasm of glomerulus, tubular epithelial cells, interstitium and vascular endothelium. CONCLUSIONS: P-selectin might mediate intraglomerular platelets aggregation, activation and leukocyte accumulation in the early stages of human proliferative glomerulonephritis. The up-regulation of P-selectin in interstitium was associated with interstitial fibrosis and tubular atrophy and may contribute to the progression of glomerulonephritis.

Adult↗
PubMed1998

Differential expression and function of L-selectin on CD56bright and CD56dim natural killer cell subsets.

NK cells are the first line of defense against foreign cells, virally infected cells, and tumors. The mechanisms whereby NK cells accumulate in extralymphoid sites in response to pathogenic stimuli are not well understood. The L-selectin adhesion molecule (CD62L) plays a primary role in mediating the initial interaction of leukocytes with vascular endothelium, a crucial step in the extravasation of immune effector cells into tissues. In this report, we show L-selectin to be uniquely expressed on a subset of resting human NK cells (CD56bright). Notably, CD56bright NK cells expressed L-selectin at a higher density than all other peripheral blood leukocytes. NK activation by PMA, IL-2, IL-15, or TGF-beta down-regulated L-selectin on the CD56bright subset, while increased L-selectin levels were observed in both the CD56bright and CD56dim NK subsets in response to IL-12, IL-10, or IFN-alpha. Moreover, CD56bright NK cells bound with high efficiency to physiologic L-selectin ligands on peripheral lymph node high endothelial venules (HEV). In sharp contrast, CD56dim NK cells adhered poorly to HEV and were predominantly L-selectin- or expressed L-selectin only at low density. In CD56bright cells and a subpopulation of CD56dim cells, L-selectin ligation by mAb cross-linking activated lymphocyte function-associated Ag 1 (LFA-1), a second adhesion molecule required for leukocyte extravasation. LFA-1 was expressed on both NK subsets, although its density was constitutively higher on CD56dim cells. Taken together, evidence of differential expression of L-selectin and LFA-1 on CD56bright and CD56dim NK subsets strongly suggests unique migratory properties and functions of these cells during the early immune response to foreign pathogens.

3T3 Cells↗
PubMed1998

Expression of P-selectin on hepatic endothelia and platelets promoting neutrophil removal by liver macrophages.

The role of P-selectin on polymorphonuclear leukocyte (PMN) adhesion-induced PMN elimination in the liver is unclear. Our objectives were to show the expression and distribution of P-selectin in rat liver, as well as to evaluate the changes in the modulation of the expression of P-selectin and its role in the accumulation and sequestration of PMNs. The intravenous administration of endotoxin markedly increased the expression of P-selectin on the venous and sinusoidal endothelial cells, as well as on the platelets trapped in the liver. Its expression peaked at 6 hours postinjection and was associated with a rapid increase in the aggregation and elimination of PMNs in the hepatic sinusoids. Combined treatment with an antibody to P-selectin or with low molecular weight heparin, a P-selectin antagonist, blocked the P-selectin, significantly reduced the arrest of PMNs, and delayed their removal in the liver. Pretreatment with gadolinium chloride inhibited phagocytosis of PMNs by the Kupffer cells, decreased the expression of P-selectin, and limited the hepatic accumulation of PMNs. Thus, P-selectin played a role in accumulation and elimination of PMNs from the liver. Results also suggest that activated Kupffer cells can modulate the expression of P-selectin in the liver and influence the homeostasis of PMNs in the circulation during acute inflammation.

Animals↗
PubMed1998

Adenosine triphosphate-induced shedding of CD23 and L-selectin (CD62L) from lymphocytes is mediated by the same receptor but different metalloproteases.

CD23 is a transmembrane protein expressed on the surface of B-lymphocytes that binds IgE, CD21, CD11b, and CD11c. High concentrations of soluble CD23 and L-selectin are found in the serum of patients with B-chronic lymphocytic leukemia (B-CLL). Because extracellular adenosine triphosphate (ATP) causes shedding of L-selectin via activation of P2Z/P2X7 receptors expressed on B-CLL lymphocytes, we studied the effect of ATP on shedding of CD23. ATP-induced shedding of CD23 at an initial rate of 12% of that for L-selectin, whereas the EC50 for ATP was identical (35 micromol/L) for shedding of both molecules. Furthermore, benzoylbenzoyl ATP also produced shedding of CD23 and L-selectin with the same agonist EC50 values for both (10 micromol/L). Inactivation of the P2Z/P2X7 receptor by preincubation with oxidized ATP abolished ATP-induced shedding of both molecules. Moreover, KN-62, the most potent inhibitor for the P2Z/P2X7 receptor, inhibited ATP-induced shedding of both CD23 and L-selectin with the same IC50 (12 nmol/L). Ro 31-9790, a membrane permeant zinc chelator that inhibits the phorbol-ester-stimulated shedding of L-selectin, also inhibited shedding of CD23 from B-CLL lymphocytes. However, the IC50 for this inhibition by Ro31-9790 was different for L-selectin and CD23 (83 v 6 micromol/L, respectively). Although L-selectin was completely shed by incubation of cells with phorbol-ester, CD23 was not lost under these conditions. The data show that extracellular ATP induces shedding of L-selectin and CD23 from B-CLL lymphocytes by an action mediated by the P2Z/P2X7 receptor. However, different membrane metalloproteases seem to mediate the shedding of L-selectin and CD23.

Adenosine Triphosphate↗