UMLS:C0001511 - FACTA Search

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Query: UMLS:C0001511 (Adhesion)
5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adhesion to collagen was investigated as a function of platelet age in rat platelets. Platelet adherence was measured using EDTA-containing platelet- rich plasma which was added to preparations of collagen fibers clamped between magnetic stirrers by recording changes in light transmission. The plot of light transmission versus logarithm of time was linear and allowed calculation of a slope factor which related to the rate of adherence. Neither the amount of collagen nor the platelet count were limiting in the test. Young platelet populations (less than or equal to 1 day old) were obtained during the recovery phase from immune induced thrombocytopenia. Old platelet populations were prepared by blocking thrombopoiesis with cyclophosphamide. Young platelets showed a moderate but statistically significant increase in adhesivity to collagen but old platelets did not differ significantly from randomly aged platelets in this function. The electrophoretic mobility of platelets was not affected by their age.
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PMID:Effect of platelet age on adhesiveness to collagen and platelet surface charge. 103 40

Recently, we described a platelet antibody against a putative collagen receptor (P62), which was found in a patient with idiopathic thrombocytopenic purpura (ITP) (Blood 69:1712). We now report a deficiency of the P62 receptor in a young man whose platelets showed defective collagen-induced platelet aggregation. He had a mild bleeding tendency and slight thrombocytopenia. The results of coagulation and fibrinolysis studies were normal. The patient's platelets were partially unresponsive to collagen, although aggregation in response to ADP, thrombin, ristocetin, and calcium ionophore (A23187) was almost normal. Adhesion of his platelets to bovine collagen was markedly reduced. Addition of collagen caused no synthesis of thromboxane (TX)B2 in platelet rich plasma (PRP) from this patient. Furthermore, collagen produced no rise of cytosolic free calcium ([Ca2+]i) in fura2-loaded platelets. In contrast, thrombin caused TXB2 formation and an increase of [Ca2+]i in his platelets. These results suggest defective interaction between the platelets and collagen. The IgG from the ITP-patient induced irreversible aggregation in normal PRP, but caused no aggregation of the young man's platelets. Immunoblot studies showed that normal platelets had antigens with a molecular weight of 62 KDa under reducing conditions and of 57 KDa under nonreducing conditions. In contrast, the young man's platelets had no P62 band, although GPIa/IIa and thrombospondin were normally present. These results indicate that impaired collagen-induced aggregation in the patient's platelets was due to a deficiency of P62 and confirm that P62 may play a crucial role as a collagen receptor in platelet activation.
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PMID:Deficiency of P62, a putative collagen receptor, in platelets from a patient with defective collagen-induced platelet aggregation. 131 Nov 44

Adhesion to endothelial cells by blood cells was assessed by measuring the cell number of each blood cell component in the supernatant after exposing blood cells to dengue-infected endothelial cells for 0, 10, 20 and 30 minutes. White blood cells, neutrophils, lymphocytes, platelets, and large lymphocytes or large unstained cells (LUC) preferentially bound to dengue-infected endothelial cells as compared to the control endothelial cells. P values were 0.0096 for total leukocytes and platelets, 0.006 for lymphocytes, and 0.001 for neutrophils and LUC. Monocytes basophils and eosinophils had no interaction with dengue-infected endothelial cells. The increased binding of neutrophil and platelet to endothelial cell may explain neutropenia and thrombocytopenia in DHF patients.
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PMID:Dengue virus and endothelial cell: a related phenomenon to thrombocytopenia and granulocytopenia in dengue hemorrhagic fever. 788 87

The role of platelets and thrombin was examined in tumor cell adhesion in vitro and metastasis in vivo. Adhesion of tumor cells to platelets was inhibited by agents inhibiting platelet integrin IIb-IIIa receptor occupancy (MoAb 10E5 and tetrapeptide RGDS) as well as IIb-IIIa ligands (polyclonal antibodies against fibronectin and von Willebrand factor (vWF)). In vivo murine experimental pulmonary metastasis (tail vein injection) could be inhibited by antibody-induced induction of thrombocytopenia and reconstituted by simultaneous injection of human platelets. Preincubation of human platelets with MoAb 10E5 (vs IIb-IIIa) inhibited reconstitution of metastasis. Thrombin activates tumor cell adhesion to platelets by activating platelets as well as tumor cells. Thrombin-activated tumor cells also enhance their adhesion to endothelial cells as well as adhesive ligands fibronectin and vWF. Experimental pulmonary metastasis is enhanced 4-400 fold by preinfusion of thrombin into mice or 10-160 fold by prior treatment of tumor cells with thrombin. The in vitro and in vivo effects of thrombin were mimicked by thrombin receptor activation peptides SFLLRNPNDKYEPF and SFLLRN. Nine of nine tumor cell lines have the seven transmembrane spanning thrombin receptor detected by the polymerase chain reaction. Thus, both platelets and thrombin contribute to experimental tumor metastasis by fostering and enhancing IIb-IIIa integrin platelet interaction with tumor cells. Since many tumor cells generate thrombin, it is proposed that tumor cells may autoactivate a metastatic phenotype.
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PMID:Role of platelets, thrombin, integrin IIb-IIIa, fibronectin and von Willebrand factor on tumor adhesion in vitro and metastasis in vivo. 857 73

Adhesion molecules are critical in the cellular interactions involved in specific immune responses. They are used for homing, cell migration, cell-cell contact and, in some cases, for the delivery of costimulatory signals. Since the host-versus-graft (HVG) reaction represents a particular form of T-B-cell interaction, we have explored whether the inhibition of lymphocyte function-associated antigen-1/intracellular adhesion molecule-1 (LFA-1/ICAM-1) interactions and the signalling through very late activation antigen-4 (VLA-4) have any effect on the development of a lupus-like disease in BALB/c mice injected at birth with (BALB/cxC57BL/6)F1 spleen cells. In close association with the development of tolerance to donor allografts, these mice show a polyclonal activation of F1 donor B cells by alloreactive host CD4+ T cells, manifested by the production of autoantibodies (autoAbs) and the development of a mild glomerulonephritis. The dose of the monoclonal antibody (mAb) employed has been adjusted to block completely the molecule on the surface of peripheral lymphocytes without interfering with the induction of neonatal tolerance. Injection of saturating doses (100 microg/2 days) of either anti-LFA-1alpha or anti-ICAM-1 mAbs, but not anti-VLA-4alpha or anti-LFA-1beta mAbs, blocks the production of anti-ssDNA autoAbs and the thrombocytopenia characteristic of this HVG disease (HVGD). However, anti-VLA-4alpha treatment is only able to delay the production of autoAbs and the anti-LFA-1beta treatment, not to modify the evolution of the HVGD. These results point to the relevance of LFA-1/ICAM-1 interactions, but not of the VLA-4-mediated signal, in the polyclonal B-cell activation occurring during the allogeneic interactions between host T helper type 2 cells and donor B cells in HVGD.
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PMID:Different roles for LFA-1 and VLA-4 integrins in T-B-cell interactions in vivo. 1044 65

This study demonstrates that the human platelet F11 receptor (F11R) functions as an adhesion molecule, and this finding is confirmed by the structure of the protein as revealed by molecular cloning. The F11R is a 32-/35-kd protein duplex that serves as the binding site through which a stimulatory monoclonal antibody causes platelet aggregation and granule secretion. A physiological role for the F11R protein was demonstrated by its phosphorylation after the stimulation of platelets by thrombin and collagen. A pathophysiological role for the F11R was revealed by demonstrating the presence of F11R-antibodies in patients with thrombocytopenia. Adhesion of platelets through the F11R resulted in events characteristic of the action of cell adhesion molecules (CAMs). To determine the structure of this protein, we cloned the F11R cDNA from human platelets. The predicted amino acid sequence demonstrated that it is an integral membrane protein and an immunoglobulin superfamily member containing 2 extracellular C2-type domains. The structure of the F11R as a member of a CAM family of proteins and its activity in mediating adhesion confirm each another. We conclude that the F11R is a platelet-membrane protein involved in 2 distinct processes initiated on the platelet surface. The first is antibody-induced platelet aggregation and secretion that are dependent on both the FcgammaRII and the GPIIb/IIIa integrin and that may be involved in pathophysiological processes associated with certain thrombocytopenias. The second is an F11R-mediated platelet adhesion that is not dependent on either the FcgammaRII or the fibrinogen receptor and that appears to play a role in physiological processes associated with platelet adhesion and aggregation. (Blood. 2000;95:2600-2609)
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PMID:Cloning of the human platelet F11 receptor: a cell adhesion molecule member of the immunoglobulin superfamily involved in platelet aggregation. 1075 40

We and others have recently defined that Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1/CD31) functions as a negative regulator of platelet-collagen interactions involving the glycoprotein VI/Fc receptor gamma chain (GPVI/FcR-gamma chain) signaling pathway.1,2 In this study, we hypothesized that PECAM-1 may be physically and functionally associated with Fc gamma RIIa on the platelet membrane. The functional relationship between PECAM-1 and Fc gamma RIIa was assessed by determining the effect of anti-PECAM-1 monoclonal antibody Fab fragments on Fc gamma RIIa-mediated platelet aggregation and heparin-induced thrombocytopenia (HITS)-mediated platelet aggregation. Preincubation of washed platelets with monoclonal antibody fragments of 2BD4 directed against PECAM-1 and IV.3 directed against Fc gamma RIIa completely blocked Fc gamma RIIa-mediated platelet aggregation and HITS-mediated platelet aggregation, whereas anti-CD151 antibody had no blocking effect. Coengagement of Fc gamma RIIa and PECAM-1 resulted in negative regulation of Fc gamma RIIa-mediated phospholipase C gamma 2 activation, calcium mobilization, and phosphoinositide 3-kinase-dependent signaling pathways. In addition, the physical proximity of Fc gamma RIIa and PECAM-1 was confirmed by using fluorescence resonance energy transfer and coimmunoprecipitation studies. These results indicate that PECAM-1 and Fc gamma RIIa are colocalized on the platelet membrane and PECAM-1 down-regulates Fc gamma RIIa-mediated platelet responses.
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PMID:Physical proximity and functional interplay of PECAM-1 with the Fc receptor Fc gamma RIIa on the platelet plasma membrane. 1289 67

Recombinant HPA-1a antibodies with Fc, mutated to remove destructive effector functions, have been developed as a potential therapy for fetomaternal alloimmune thrombocytopenia (FMAIT), via blockade of binding of human HPA-1a polyclonal antibodies to fetal HPA-1a1b platelets. We have assessed the effect of the IgG1 HPA-1a antibody B2G1 and two mutated derivatives in various functional assays in resting and agonist-stimulated platelets of the three HPA-1 genotypes. With HPA-1a1b platelets (fetal genotype), the antibodies did not activate signalling or CD62P expression in resting platelets, did not change in vitro bleeding time (IVBT), and did not inhibit platelet adhesion to collagen in flowing blood. Adhesion of HPA-1a1b platelets to fibrinogen was reduced by 20%, and aggregation induced by ADP by 50%, but collagen-related peptide (CRP-XL)-induced aggregation was normal. With HPA-1a1a platelets, aggregation to both ADP and CRP-XL was inhibited, with total blockade of adhesion to fibrinogen and of IVBT responses. Interestingly, a monovalent antibody fragment with identical specificity had no inhibitory effect on aggregation. In static adhesion assays using human alphaIIbbeta3 or alphaVbeta3 transfectants of HPA-1a (Leu(33)) phenotype, attachment to fibrinogen of the latter but not of the former was completely blocked by the HPA-1a antibodies. These observations are best explained by antibody-mediated blockade of the RGD binding site on beta3 by a mechanism of steric hindrance. As the effect on platelet function is modest with HPA-1a1b (fetal type) platelets, the mutated HPA-1a antibodies described here could be developed further for FMAIT therapy.
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PMID:The effect of recombinant IgG antibodies against the leucine-33 form of the platelet beta3 integrin (HPA-1a) on platelet function. 1504 36

Efalizumab (Raptiva, Serono) is a humanised monoclonal antibody (IgG1) produced by biotechnology. This antibody has a novel place among biotherapies for psoriasis. It is bound to the CD11a subunit of a surface molecule of the T lymphocyte LFA-1 (Leucocyte Function-associated Antigen-1). This molecule is essential for binding of T lymphocytes to the ICAM-1 molecule (Intercellular Adhesion Molecule-1) found on antigen-presenting cells, endothelial cells and keratinocytes. Binding of efalizumab to CD11a prevents binding of LFA-1 to ICAM-1, thus inhibiting several steps in the immunological process responsible for formation of psoriatic plaque (activation of naive T lymphocytes to memory T lymphocytes, lymphocyte migration and reactivation of T lymphocytes in skin). Efalizumab was approved in the United States by the FDA (Food and Drug Administration) in 2003 for the treatment of moderate-to-severe psoriasis requiring systemic therapy. It may be used as first-line therapy in the United States in this indication. In France, marketing authorisation (MA) was granted more recently in September 2005. The indications are moderate-to-severe cutaneous plaque psoriasis in adults in cases of failure, intolerance or contraindication of at least two systemic treatments including phototherapy, methotrexate and cyclosporine. Current clinical trial data is available for 3500 patients with plaque psoriasis. A 75% improvement in PASI score was seen in between 22 and 39% of patients treated with efalizumab (vs. 2 to 5% for patients on placebo) in a single weekly subcutaneous injection (1 mg/kg). A study in good responders confirms the continuing long-term efficacy of prescription of the drug up to 36 months (with at least a 75% improvement in PASI score in 53% of patients). However, it is not effective against joint involvement in psoriasis. The most common side-effects (incidence >1/100) are influenza-like syndrome, risk of outbreak of cutaneous psoriasis during or after discontinuation of treatment, worsening of arthralgia, minor hypersensitivity reactions, reversible changes in laboratory values (hyperlymphocytosis, elevated alkaline phosphatases and transaminases). Because of rare cases of thrombocytopenia (incidence<1/100), reversible on discontinuation of treatment, monthly monitoring of platelet counts is required over the first 3 months of therapy. There are currently no randomised studies comparing the various systemic treatments (standard therapy and biotherapy) for psoriasis. However, on extrapolation of the available results concerning efficacy (PASI-75 after 12 weeks of treatment), efalizumab appears to be less efficacious than anti-TNF alpha agents. This drug constitutes an additional treatment option and its position in the therapeutic arsenal will depend upon its long-term benefit/risk ratio in relation to other biotherapies.
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PMID:[Efalizumab]. 1705 36

Adhesion properties of hematopoietic stem cells (HSCs) in the bone marrow (BM) niches control their migration and affect their cell-cycle dynamics. The serum response factor (Srf) regulates growth factor-inducible genes and genes controlling cytoskeleton structures involved in cell spreading, adhesion, and migration. We identified a role for Srf in HSC adhesion and steady-state hematopoiesis. Conditional deletion of Srf in BM cells resulted in a 3-fold expansion of the long- and short-term HSCs and multipotent progenitors (MPPs), which occurs without long-term modification of cell-cycle dynamics. Early differentiation steps to myeloid and lymphoid lineages were normal, but Srf loss results in alterations in mature-cell production and severe thrombocytopenia. Srf-null BM cells also displayed compromised engraftment properties in transplantation assays. Gene expression analysis identified Srf target genes expressed in HSCs, including a network of genes associated with cell migration and adhesion. Srf-null stem cells and MPPs displayed impair expression of the integrin network and decreased adherence in vitro. In addition, Srf-null mice showed increase numbers of circulating stem and progenitor cells, which likely reflect their reduced retention in the BM. Altogether, our results demonstrate that Srf is an essential regulator of stem cells and MPP adhesion, and suggest that Srf acts mainly through cell-matrix interactions and integrin signaling.
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PMID:The transcription factor Srf regulates hematopoietic stem cell adhesion. 2070 9

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