Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

All trans-retinoic acid (ATRA) induces complete remission in acute-promyelocytic-leukemia (APL) patients. This study investigated the adhesive properties of APL cells for the endothelium and the extracellular matrix, their motility and the effect of ATRA on these functions. Blasts from 7 APL patients adhered to resting and IL-1-activated endothelium, to the same degree as normal PMN. Adhesion was partially mediated by ICAM-1 and, for IL-1-activated endothelium, by VCAM-1 and E-selectin. These cells showed less adhesiveness for the matrix than PMN, although they maintained the same substrate preference: they adhered to fibronectin and thrombospondin, but not to laminin and type-IV collagen. Exposure to ATRA in vitro (1 microM for 48 to 96 hr) increased the adhesiveness of APL cells; this effect was particularly evident in the case of sub-endothelial matrix and fibronectin. A similar increment in adhesiveness was observed when comparing cells from 2 patients before and after treatment with ATRA. APL cells migrated in response to fMLP and motility was increased by ATRA. In conclusion, APL cells were less adhesive to the matrix than PMN, but treatment with ATRA considerably enhanced their adhesive properties. This could be important in determining the efflux of leukemic cells from the bone marrow and their tissue infiltration during ATRA therapy.
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PMID:Effect of all trans-retinoic acid (ATRA) on the adhesive and motility properties of acute promyelocytic leukemia cells. 898 93

We have previously reported that propolypeptide of von Willebrand factor (pp-vWF) promotes melanoma cell adhesion in a beta1 integrin-dependent manner. In this report, we identified the alpha subunit of the cell adhesion receptor for pp-vWF as alpha4. Human leukemia cell lines that express alpha4beta1 integrin (very late antigen-4, VLA-4), but not cell lines which lack VLA-4, attached well to pp-vWF substrate and these adhesions were completely inhibited by anti-alpha4 integrin monoclonal antibody HP2/1. Adhesion of mouse melanoma expressing alpha4 integrin was also inhibited by anti-mouse alpha4 mAb PS/2. Furthermore, transfection of human alpha4 cDNA into alpha4(-) Chinese hamster ovary cells resulted in an acquisition of adhesive activity to pp-vWF, indicating that pp-vWF is a ligand for VLA-4 integrin. Using a recombinant fragment of pp-vWF, the cell attachment site was shown to be located within amino acid residues 376-455 of pp-vWF. A series of synthetic peptides covering this region were tested for the ability to promote cell attachment and a 15-residue peptide designated T2-15 (DCQDHSFSIVIETVQ, residues numbered 395-409) promoted VLA-4 dependent cell adhesion. The peptide was also capable of inhibiting cell adhesion to pp-vWF, suggesting that this sequence represents the cell attachment site. By affinity chromatography using peptide T2-15-Sepharose, it was found that alpha4beta1 integrin complex from extracts of surface iodinated B16 cells specifically bound to the peptide. These results strongly suggest that pp-vWF is a novel physiological ligand for VLA-4.
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PMID:Propolypeptide of von Willebrand factor is a novel ligand for very late antigen-4 integrin. 907 71

Rat basophilic leukemia cells will adhere to and spread out on fibronectin coated surfaces in an integrin dependent manner. Adhesion and spreading on fibronectin leads to increased degranulation, inositol phosphate production, phospholipase D activation, and increased production of prostaglandin D2 and leukotriene C4 when the cells are activated through the high affinity IgE receptor. Rat basophilic leukemia cells will also adhere to surfaces coated with anti-rat class I antibodies, poly-L-lysine, and a lectin purified from Tetragonolobus purpureas. In all cases, antigen activated cells, which were adherent, displayed increased signaling, degranulation and eicosanoid production as compared to cells which were non-adherent. Cells which adhere to either anti-rat class I antibodies or poly-L-lysine also spread even though this is not mediated through integrins. In contrast, adhesion to the lectin from Tetragonolobus did not cause any appreciable spreading unless the cells were also triggered through the IgE receptor. Cells were also able to bind to fibronectin immobilized on polystyrene beads which mimics adhesion but does not allow spreading. However, these cells exhibited no increased signaling, degranulation, or eicosanoid production. Furthermore, rat basophilic leukemia cells can be modified by incubating them in the presence of biotinylated-phosphatidylserine which becomes incorporated into the membrane. These modified cells will adhere to streptavidin coated plates while unmodified cells will not. However, these modified cells do not spread, even after activation with antigen, and they show no increased degranulation or production of eicosanoids. These results indicate that adhesion itself is not sufficient for upregulation of the cells in response to antigen and that spreading of the cells may be the critical component.
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PMID:Increased degranulation and phospholipase A2, C, and D activity in RBL cells stimulated through FcepsilonR1 is due to spreading and not simply adhesion. 909 51

Adhesion of normal colony-forming cells (CFC) to bone marrow (BM) stroma and the extracellular matrix (ECM) component fibronectin (FN) depends at least in part on the alpha4beta1 and alpha5beta1 integrins and the CD44 receptor. Aside from anchoring progenitors in the marrow microenvironment, beta1 integrin-dependent adhesion of normal CFC is associated with inhibition of their proliferation. In contrast to normal CFC, chronic myelogenous leukemia (CML) Ph+ CFC adhere significantly less to either stroma or FN. CML Ph+ CFC proliferation is also not inhibited by coculture with stroma or FN. However, equal numbers of alpha4, alpha5, and beta1 integrins and CD44 are present on CML and normal CD34+ cells. We have previously demonstrated that beta1-dependent adhesion to and subsequent proliferation inhibition by FN can be restored when CML Ph+ CFC are incubated with the beta1 integrin activating antibody, 8A2, and demonstrated a role for the alpha5beta1 integrin in this phenomenon. Since the integrin alpha4beta1 and the proteoglycan form of CD44 may cooperate in establishing normal CFC adhesion to FN, we examined if treatment of CML Ph+ CFC with 8A2 also restores the cooperativity between beta1 integrins and CD44. We demonstrate that 8A2 induces adhesion of CML Ph+ CFC not only to intact FN but also to alpha4beta1, alpha5beta1, and proteoglycan binding fragments of FN. 8A2-induced adhesion to these fragments and peptides also results in a significant inhibition of the proliferation of CML Ph+ CFC. Addition of antibodies to either the alpha5, alpha4, or beta1 integrins, antibodies against the CD44 receptor, or removal of chondroitin sulfate glycosaminoglycans from the surface of CML CD34+ HLA-DR+ cells significantly reduced the 8A2-induced adhesion to and adhesion-mediated inhibition of proliferation by FN. These studies demonstrate that activation of beta1 integrins on CML Ph+ CFC not only results in upregulation of beta1 integrin-dependent adhesion and adhesion-mediated inhibition of proliferation, but also in the restoration of cooperation between beta1 integrins and CD44. These studies suggest that decreased beta1 integrin avidity may also affect the function of the proteoglycan adhesion receptor CD44, both of which may contribute to the abnormal circulation and expansion of malignant progenitors in CML.
Leukemia 1997 Jun
PMID:Activation of beta1 integrins on CML progenitors reveals cooperation between beta1 integrins and CD44 in the regulation of adhesion and proliferation. 917 35

Recent reports have shown that leukocyte-leukocyte adhesion is dependent on L-selectin and that leukocyte recognition of L-selectin may be mediated by P-selectin glycoprotein ligand-1 (PSGL-1). We show that the specific attachment and rolling of human neutrophils and the leukemia cell lines HL-60 and U937 on immobilized, purified L-selectin under continuous shear stress is only partially inhibited by treatment with the PSGL-1 monoclonal antibody (MoAb), KPL1 (41% to 53% inhibition), suggesting that L-selectin ligand activity in addition to PSGL-1 may mediate myeloid cell rolling on L-selectin. K562 cells cotransfected with cDNAs encoding alpha (1,3)fucosyltransferase-VII (FucT-VII) and PSGL-1 rolled on L-selectin. Adhesion of FucT-VII-PSGL-1 transfectants to L-selectin was completely blocked by MoAb KPL1, indicating that both L-selectin and P-selectin bind similar sites on PSGL-1. In support of existence of a non-PSGL-1 L-selectin ligand activity on leukocytes, an HL-60 membrane preparation immunodepleted of PSGL-1 supported rolling of L-selectin, but not P-selectin transfectants. Treatment of HL-60 cells with O-sialoglycoprotein endopeptidase inhibited attachment and rolling on L-selectin and P-selectin. However, neuraminidase treatment completely blocked HL-60 rolling on L-selectin, but not P-selectin, suggesting L-selectin and P-selectin ligand activities have different contributions of sialic acid. These findings indicate that myeloid cells express sialylated, O-linked glycoprotein ligand activity independent of PSGL-1 that supports L-selectin-mediated rolling.
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PMID:Functional characterization of L-selectin ligands on human neutrophils and leukemia cell lines: evidence for mucinlike ligand activity distinct from P-selectin glycoprotein ligand-1. 944 70

Development of the hematopoietic lineages is partially under the control of hematopoietic receptors with tyrosine kinase activity (RTK). To compare the cellular functions of two of the class III RTK, FLT3 and KIT, a murine chimeric FMS/FLT3 (FF3) receptor was expressed ectopically using retroviral infection, in normal IL3-derived cultured mast cells. Stimulation of the chimeric receptor produced a full mitogenic signal and led to mast cell maturation, as occurs upon activation of the endogenous KIT receptor. When introduced into mast cells derived from KIT-deficient White spotting (W) mutant mice, the FF3 receptor bypassed their mitogenic defect. KIT activation induced a synergistic mitogenic activity in mast cells upon IL3 stimulation, whereas FF3 appeared to down-modulate the IL3 response. Adhesion to fibronectin was specifically associated with KIT signaling.
Leukemia 1998 Jul
PMID:Specific and common activities of the FLT3 and KIT tyrosine kinase receptors revealed by the use of cultured mast cells. 966 95

Antigen-antibody systems provide the flexibility of varying the kinetics and affinity of molecular interaction and studying the resulting effect on adhesion. In a parallel-plate flow chamber, we measured the extent and rate of adhesion of rat basophilic leukemia cells preincubated with anti-dinitrophenyl IgE clones SPE-7 or H1 26. 82 to dinitrophenyl-coated polyacrylamide gel substrates in a linear shear field. Both of these IgEs bind dinitrophenyl, but H1 26.82 has a 10-fold greater on rate and a 30-fold greater affinity. Adhesion was found to be binary; cells either arrested irreversibly or continued at their unencumbered hydrodynamic velocity. Under identical conditions, more adhesion was seen with the higher affinity (higher on rate) IgE clone. At some shear rates, adhesion was robust with H1 26.82, but negligible with SPE-7. Reduction in receptor number or ligand density reduced the maximum level of adhesion seen at any shear rate, but did not decrease the shear rate at which adhesion was first observed. The spatial pattern of adhesion for both IgE clones is well represented by the first-order kinetic rate constant kad, and we have determined how kad depends on ligand and receptor densities and shear rate. The rate constant kad found with H1 26.82 was approximately fivefold greater than with SPE-7. The dependence of kad on site density and shear rate for SPE-7 is complex: kad increases linearly with antigen site density at low to moderate shear rates, but is insensitive to site density at high shear. kad increases with shear rate at low site density but decreases with shear at high site density. With H1 26.82, the functional dependence of kad with shear rate was similar. Although these data are consistent with the hypothesis that we have sampled both transport and reaction-limited adhesion regimes, they point out deficiencies in current theories describing cell attachment under flow.
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PMID:Kinetics of adhesion of IgE-sensitized rat basophilic leukemia cells to surface-immobilized antigen in Couette flow. 978 56

Chronic myelogenous leukemia (CML) originates in a pluripotent hematopoietic stem cell of the bone marrow and is characterized by greatly increased numbers of granulocytes in the blood. Myeloid and other hematopoietic cell lineages are involved in the process of clonal proliferation and differentiation. After a period of 4-6 years the disease progresses to acute-stage leukemia. On the cellular level, CML is associated with a specific chromosome abnormality, the t(9; 22) reciprocal translocation that forms the Philadelphia (Ph) chromosome. The Ph chromosome is the result of a molecular rearrangement between the c-ABL proto-oncogene on chromosome 9 and the BCR (breakpoint cluster region) gene on chromosome 22. Most of ABL is linked with a truncated BCR. The BCR/ABL fusion gene codes for an 8-kb mRNA and a novel 210-kDa protein which has higher and aberrant tyrosine kinase activity than the normal c-ABL-coded counterpart. Phosphorylation of a number of substrates such as GAP, GRB-2, SHC, FES, CRKL, and paxillin is considered a decisive step in transformation. An etiological connection between BCR/ABL and leukemia is indicated by the observation that transgenic mice bearing a BCR/ABL DNA construct develop leukemia of B, T, and myeloid cell origin. CML cells proliferate and expand in an almost unlimited manner. Adhesion defects in bone marrow stromal cells have been proposed to explain the increased number of leukemic cells in the peripheral blood. However, findings of our laboratory have shown that the BCR/ABL chimeric protein that is expressed in transfected cells may, under certain conditions, also increase the adhesion to fibronectin via enhanced expression of integrin. Our previous immunocytological studies on the expression of beta1 and beta2 integrins have found no qualitative differences between normal and CML hematopoietic cells in vitro. Even long-term-cultured CML bone marrow or blood cells continuously express those adhesion molecules that are characteristic of the cytological type. Recent experiments indicate that certain early CML progenitors may adhere to the stromal layer in vitro similarly to their normal counterparts. They cannot be completely removed by long-term culture on allogeneic stromal cells. At present, the only curative therapy is transplantation of allogeneic hematopoietic stem cells. Based on the molecular and cellular state of knowledge of CML, new therapies are being developed. BCR/ABL antisense oligonucleotides, inhibitors of tyrosine kinase, peptide-specific adoptive immunotherapy or peptide vaccination, and restoration of hematopoiesis by autologous stem cell transplantation following CML cell purging are examples of important approaches to improving CML treatment.
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PMID:Chronic myelogenous leukemia: molecular and cellular aspects. 987 25

Minimally differentiated acute myeloid leukemia (AML-M0) is a rare FAB subtype (2-3% of AMLs) of poor prognosis. The aim of our study was to characterize AML-M0 expression and regulation of adhesion/costimulatory molecule involved in immune recognition, to test blast in vitro immunogenicity, and to determine the percentage of leukemia progenitor cells. Here, we demonstrate that alloimmune recognition of AML-M0 in primary mixed lymphocyte reaction, as evaluated by IL-2 secretion of responding T cells, is reduced in comparison with more differentiated subtypes (128 +/- 95 pg/ml vs304 +/- 159 pg/ml, P < 0.05). These data are in line with low blast cell expression of major histocompatibility complex (MHC) class II DR molecules, and of the CD28 ligand B7-2, which plays an important role in AML immune recognition. Adhesion/costimulatory molecules were up-regulated by leukemic cell stimulation via CD40, and, although less efficiently, by gamma-IFN; both stimuli improved blast cell immunogenicity. We also demonstrate that AML-M0 have a very high percentage (40% +/- 30) of CD34+/CD38- leukemic clonogenic precursors in comparison with more differentiated AMLs (2.5% +/- 2) or non-leukemic CD34+hematopoietic precursors (1.8% +/- 0.8). Since the presence of a leukemic cell population at an early differentiation stage has been identified as a poor prognostic factor, we conclude that the high frequency of CD34+/CD38- blasts in AML-M0 may converge with already identified poor prognosis factors such as chemotherapy resistance and cytogenetic abnormalities. The clinical implications of AML-M0 impaired in vitroimmunogenicity and a high percentage of CD34+/CD38- blasts will require comparative analysis of additional patients. The increased immunogenicity of blast cells after CD40 triggering provide interesting clues for AML-M0 immunotherapy, that have to be confirmed with an in vivo leukemia model in mice.
Leukemia 1999 Oct
PMID:The immunophenotype of minimally differentiated acute myeloid leukemia (AML-M0): reduced immunogenicity and high frequency of CD34+/CD38- leukemic progenitors. 1051 51

The adhesive function of integrins is regulated through cytoplasmic signaling. The present study was performed to investigate the relevance of cytoplasmic signaling and cytoskeletal assembly to integrin-mediated adhesion induced by chemokines. Adhesion of T cells induced by chemokines macrophage inflammatory protein (MIP)-1alpha and MIP-1beta was inhibited by pertussis toxin, wortmannin, and cytochalasin B, suggesting that both G protein-sensitive phosphatidylinositol (PI) 3-kinase activation and cytoskeletal assemblies are involved. The chemokine-induced T cell adhesion could be mimicked by expression of small G proteins, fully activated H-RasV12, or H-RasV12Y40C mutant, which selectively binds to PI 3-kinase, in T cells, inducing activated form of LFA-1alpha and LFA-1-dependent adhesion to ICAM-1. H-Ras expression also induced F-actin polymerization which colocalized with profilin in T cells. Adult T cell leukemia (ATL) cells spontaneously adhered to ICAM-1, which depended on endogenous MIP-1alpha and MIP-1beta through activation of G protein-sensitive PI 3-kinase. H-Ras signal pathway, leading to PI 3-kinase activation, also induced active configuration of LFA-1 and LFA-1-mediated adhesion of ATL cells, whereas expression of a dominant-negative H-Ras mutant failed to do. Profilin-dependent spontaneous polymerization of F-actin in ATL cells was reduced by PI 3-kinase inhibitors. In this paper we propose that H-Ras-mediated activation of PI 3-kinase can be involved in induction of LFA-1-dependent adhesion of T cells, which is relevant to chemokine-mediated signaling, and that profilin may form an important link between chemokine- and/or H-Ras-mediated signals and F-actin polymerization, which results in triggering of LFA-1 on T cells or leukemic T cells.
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PMID:H-Ras signals to cytoskeletal machinery in induction of integrin-mediated adhesion of T cells. 1057 Mar 13


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