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PubMed1992

A new method for promoting adhesion between precious metal alloys and dental adhesives.

A new, simple method of modifying the adherend metal surface by a liquid Ga-Sn alloy (Adlloy) was applied to dental precious and base-metal alloys for adhesion with 4-META adhesive resin. Adhesions of 4-META resin to three other surface states--as-polished, oxidized at high temperature, and electroplated tin--were also performed for comparison with the adhesion on Adlloy-modified surfaces. Bond strength measurements were made, and the durability against water at the adhering interface was evaluated. The Adlloy-modified gold alloys (Type IV and 14 K) and silver-based alloys (Ag-Pd and Ag-Cu) showed not only high bond strengths but also excellent water durability at the adhesion interface. Surface modification by Adlloy, however, did not affect adhesion to Ag-In-Zn and base-metal (SUS, Co-Cr, and Ni-Cr) alloys. Adhesion to the tin-electroplated specimens was comparable with that to the Adlloy-modified specimens.

Acrylic Resins↗

PubMed2001

Platelet/polymorphonuclear leukocyte adhesion: a new role for SRC kinases in Mac-1 adhesive function triggered by P-selectin.

Adhesion of polymorphonuclear leukocytes (PMNLs) to activated platelets requires a P-selectin-triggered, tyrosine kinase-dependent adhesiveness of Mac-1 and is accompanied by tyrosine phosphorylation of a 110-kd protein (P-110) in PMNLs. Inhibitors of SRC tyrosine kinases were found to inhibit PMNL adhesion to activated platelets or to P-selectin expressing Chinese hamster ovary (CHO-P) cells and the tyrosine phosphorylation of P-110. Adhesion of PMNLs to activated platelets or to CHO-P cells stimulated activity of LYN and HCK. Monoclonal antibody blockade of P-selectin or beta2-integrins reduced the activation of both kinases. In PMNLs either adherent to platelets or aggregated by P-selectin-IgG chimera, Mac-1 was rapidly redistributed to the Triton X-100-insoluble cytoskeletal fraction, and large clusters of Mac-1 colocalized with patches of F-actin at the sites of cell-cell contact. In PMNLs stimulated by P-selectin-IgG chimera, SRC kinase inhibition impaired Mac-1 clustering, F-actin accumulation, and CD18 redistribution to the cytoskeleton. Disruption of the actin filament network by cytochalasin D prevented PMNL-platelet adhesion and P-selectin-induced PMNL aggregation and impaired the clustering of Mac-1. In agreement with the requirement for the beta2-integrin in the functional up-regulation of LYN and HCK, integrin blockade by monoclonal antibodies resulted in a complete inhibition of P-selectin-induced Mac-1 clustering and F-actin accumulation. Taken together, the results indicate that, after an initial P-selectin-triggered beta2-integrin interaction with the ligand, SRC kinases are activated and allow the remodeling of cytoskeleton-integrin linkages and integrin clustering that finally strengthen cell-cell adhesion. This model highlights a new role for SRC kinases in a regulatory loop by which the Mac-1 promotes its own adhesive function.

Actins↗

PubMed2002

Class A scavenger receptors mediate cell adhesion via activation of G(i/o) and formation of focal adhesion complexes.

Class A macrophage scavenger receptors (SR-A) are multifunctional receptors with roles in modified lipoprotein uptake, innate immunity, and macrophage adhesion. Our previous studies conducted in mouse peritoneal macrophages demonstrated that pertussis toxin (PTX) mediated inhibition of G(i/o) attenuated SR-A-dependent uptake of modified lipoprotein. The finding that SR-A-mediated lipoprotein internalization was PTX-sensitive led us to hypothesize that SR-A-mediated cell adhesion might be similarly regulated by G(i/o)-dependent signaling pathways. To test this hypothesis, SR-A was expressed in HEK cells under inducible control. Relative to HEK cells that lack SR-A, SR-A expressing cells displayed enhanced adhesion to tissue culture dishes. SR-A-mediated adhesion was significantly reduced following PTX treatment and was insensitive to chelating divalent cations with EDTA. SR-A-expressing cells exhibited a distinct cell morphology characterized by fine filopodia-like projections. Both polymerized actin and vinculin were codistributed with SR-A in the filopodia-like projections indicating the formation of focal adhesion complexes. Overall, our results indicate that the ability of SR-A to enhance cell adhesion involves G(i/o) activation and formation of focal adhesion complexes.

Actins↗

PubMed2004

Pituitary tumor-derived fibroblast growth factor receptor 4 isoform disrupts neural cell-adhesion molecule/N-cadherin signaling to diminish cell adhesiveness: a mechanism underlying pituitary neoplasia.

We previously identified pituitary tumor-derived fibroblast growth factor receptor 4 (ptd-FGFR4), an alternatively transcribed N-terminally truncated cytoplasmic receptor isoform. Unlike wild-type FGFR4, ptd-FGFR4 facilitates cell transformation and results in pituitary tumor formation in transgenic mice. To investigate differences in the tumorigenic properties of FGFR4 and ptd-FGFR4, we examined their abilities to modulate cell adhesiveness. Introduction of ptd-FGFR4 into GH4 pituitary cells or NIH 3T3 fibroblasts resulted in significant reduction in cell adhesion to a collagen IV matrix compared with FGFR4- or empty vector-transfected cells. This adhesive difference was evident in the absence or presence of FGF stimulation. Furthermore, treatment with beta1-integrin neutralizing antibody markedly reduced adhesiveness in FGFR4-transfected cells but had little effect on the depressed adhesiveness of ptd-FGFR4-transfected cells. Unlike wild-type FGFR4, ptd-FGFR4 does not associate with neural cell-adhesion molecule (NCAM). Cells expressing FGFR4 demonstrate membranous N-cadherin with a noninvasive growth pattern identical to control GH4 cells when injected into immunodeficient mice. In contrast, ptd-FGFR4-expressing cells develop invasive tumors in vivo with marked loss of N-cadherin that localizes to the cytoplasm. Consistent with these changes, beta-catenin expression was diminished and its interaction with N-cadherin was disrupted in the presence of ptd-FGFR4, but both were intact in the presence of wild-type FGFR4. These data highlight the importance of membrane-anchored FGFR4 in assembling a multiprotein FGFR4 complex with NCAM and N-cadherin playing pivotal functions in maintaining normal cell adhesion. Disruption of distinct NCAM/N-cadherin proadhesive complexes by a tumor-derived FGFR4 isoform provides a novel mechanism beyond ligand independence that explains the pathobiology of proliferative and infiltrative but nonmetastatic neoplasms.

3T3 Cells↗

PubMedDate not supplied

Influence of additional adhesive application on the microtensile bond strength of adhesive systems.

This study evaluated microtensile bond strength (pTBS) when an additional adhesive layer was applied to the dentin surface. Thirty-five human third molars were flattened to expose the occlusal dentin surface. The teeth were randomly assigned to 7 experimental groups: G1-Single Bond (SB); G2-additional layer of SB; G3--a layer of Scotchbond Multi-purpose (SMP) adhesive applied over SB; G4-Clearfil SE Bond (CE); G5-additional layer of CE; G6-Adper Prompt (AP) and G7-additional layer of AP. For the G2, G3, G5 and G7 groups, the first adhesive layer was light-cured before application of the additional layer. After bonding procedures, 5-mm high composite crowns were incrementally built up. The samples were sectioned to obtain 0.9 x 0.9 beams, which were tested under tension at a crosshead speed of 0.5-mm/minute until failure. The failure mode and adhesive thickness were evaluated under SEM. The pTBS data were analyzed by 1-way ANOVA and post-hoc Ducan's Test (a=0.05). Mean adhesive thickness was analyzed by 1-way ANOVA and post-hoc Tukey's test (a=0.05). The results indicated that G3 presented the highest microTBS and the thickest adhesive layer. G6 and G7 presented the lowest microTBS values. When solvent-free adhesives systems were used, microTBS values were not affected by the thicker layer.

Adhesiveness↗

PubMed2004

Cooperative inhibitory effects of antisense oligonucleotide of cell adhesion molecules and cimetidine on cancer cell adhesion.

AIM: To explore the cooperative effects of antisense oligonucleotide (ASON) of cell adhesion molecules and cimetidine on the expression of E-selectin and ICAM-1 in endothelial cells and their adhesion to tumor cells. METHODS: After treatment of endothelial cells with ASON and/or cimetidine and induction with TNF-alpha, the protein and mRNA changes of E-selectin and ICAM-1 in endothelial cells were examined by flow cytometry and RT-PCR, respectively. The adhesion rates of endothelial cells to tumor cells were measured by cell adhesion experiment. RESULTS: In comparison with TNF-alpha inducing group, lipo-ASON and lipo-ASON/cimetidine could significantly decrease the protein and mRNA levels of E-selectin and ICAM-1 in endothelial cells, and lipo-ASON/cimetidine had most significant inhibitory effect on E-selectin expression (from 36.37+/-1.56% to 14.23+/-1.07%, P<0.001). Meanwhile, cimetidine alone could inhibit the expression of E-selectin(36.37+/-1.56% vs 27.2+/-1.31%, P<0.001), but not ICAM-1 (69.34+/-2.50% vs 68.07+/-2.10%,P>0.05) and the two kinds of mRNA, either. Compared with TNF-alpha inducing group, the rate of adhesion was markedly decreased in lipo-E-selectin ASON and lipo-E-selectin ASON/cimetidine treated groups(P<0.05), and lipo-E-selectin ASON/cimetidine worked better than lipo-E-selectin ASON alone except for HepG2/ECV304 group (P<0.05). However, the decrease of adhesion was not significant in lipo-ICAM-1 ASON and lipo-ICAM-1 ASON/cimetidine treated groups except for HepG2/ECV304 group (P>0.05). CONCLUSION: These data demonstrate that ASON in combination with cimetidine in vitro can significantly reduce the adhesion between endothelial cells and hepatic or colorectal cancer cells, which is stronger than ASON or cimetidine alone. This study provides some useful proofs for gene therapy of antiadhesion.

Cell Adhesion↗

PubMed2002

Blockade of focal clustering and active conformation in beta 2-integrin-mediated adhesion of eosinophils to intercellular adhesion molecule-1 caused by transduction of HIV TAT-dominant negative Ras.

We transduced dominant negative (dn) HIV TAT-Ras protein into mature human eosinophils to determine the signaling pathways and mechanism involved in integrin-mediated adhesion caused by cytokine, chemokine, and chemoattractant stimulation. Transduction of TAT-dnRas into nondividing eosinophils inhibited endogenous Ras activation and extracellular signal-regulated kinase (ERK) phosphorylation caused by IL-5, eotaxin-1, and fMLP. IL-5, eotaxin-1, or fMLP caused 1) change of Mac-1 to its active conformation and 2) focal clustering of Mac-1 on the eosinophil surface. TAT-dnRas or PD98059, a pharmacological mitogen-activated protein/ERK kinase inhibitor, blocked both focal surface clustering of Mac-1 and the change to active conformational structure of this integrin assessed by the mAb CBRM1/5, which binds the activation epitope. Eosinophil adhesion to the endothelial ligand ICAM-1 was correspondingly blocked by TAT-dnRas and PD98059. As a further control, we used PMA, which activates ERK phosphorylation by postmembrane receptor induction of protein kinase C, a mechanism which bypasses Ras. Neither TAT-dnRas nor PD98059 blocked eosinophil adhesion to ICAM-1, up-regulation of CBRM1/5, or focal surface clustering of Mac-1 caused by PMA. In contrast to beta(2)-integrin adhesion, neither TAT-dnRas nor PD98059 blocked the eosinophil adhesion to VCAM-1. Thus, a substantially different signaling mechanism was identified for beta(1)-integrin adhesion. We conclude that H-Ras-mediated activation of ERK is critical for beta(2)-integrin adhesion and that Ras-protein functions as the common regulator for cytokine-, chemokine-, and G-protein-coupled receptors in human eosinophils.

CD18 Antigens↗

PubMed2003

Coexpression of CD58 or CD48 with intercellular adhesion molecule 1 on target cells enhances adhesion of resting NK cells.

The beta2 integrin LFA-1 (CD11a/CD18) mediates adhesion of lymphocytes to cells expressing ICAM. The strength of this adhesion is regulated by different signals delivered by cytokines and chemokines, and by the TCR in the case of T cells. To determine the receptor-ligand interactions required for adhesion of resting NK cells, Drosophila cells expressing different combinations of ligands of human NK cell receptors were generated. Expression of ICAM-1 alone was sufficient for an adhesion of resting NK cells that was sensitive to inhibitors of src family kinase and of phosphatidylinositol 3-kinase. Binding of resting NK cells to solid-phase ICAM-1 showed similar signaling requirements. A pulse of either IL-2 or IL-15 to resting NK cells resulted in strongly enhanced, actin-dependent adhesion to insect cells expressing ICAM-1 alone. Coexpression of either LFA-3 (CD58) or CD48 with ICAM-1 resulted in strong adhesion by resting NK cells, even in the absence of cytokines. Therefore, receptors for LFA-3 and CD48 on resting NK cells strengthen the adhesion mediated by LFA-1.

Adjuvants, Immunologic↗

PubMed1999

Lymphocyte adhesion to epithelia and endothelia mediated by the lymphocyte endothelial-epithelial cell adhesion molecule glycoprotein.

Upon encountering the relevant vascular bed, lymphocytes attach to endothelial adhesion molecules, transmigrate out of circulation, and localize within tissues. Lymphocytes may then be retained at microanatomic sites, as in tissues, or they may continue to migrate to the lymphatics and recirculate in the blood. Lymphocytes also interact transiently, but with high avidity, with target cells or APC that are infected with microbes or have taken up exogenous foreign Ags. This array of adhesive capabilities is mediated by the selective expression of lymphocyte adhesion molecules. Here, we developed the 6F10 mAb, which recognizes a cell surface glycoprotein designated lymphocyte endothelial-epithelial cell adhesion molecule (LEEP-CAM), that is distinct in biochemical characteristics and distribution of expression from other molecules known to play a role in lymphocyte adhesion. LEEP-CAM is expressed on particular epithelia, including the suprabasal region of the epidermis, the basal layer of bronchial and breast epithelia, and throughout the tonsillar and vaginal epithelia. Yet, it is absent from intestinal and renal epithelia. Interestingly, it is expressed also on vascular endothelium, especially high endothelial venules (HEV) in lymphoid organs, such as tonsil and appendix. The anti-LEEP-CAM mAb specifically blocked T and B lymphocyte adhesion to monolayers of epithelial cells and to vascular endothelial cells in static cell-to-cell binding assays by approximately 40-60% when compared with control mAbs. These data suggest a role for this newly identified molecule in lymphocyte binding to endothelium, as well as adhesive interactions within selected epithelia.

Antibodies, Blocking↗

PubMed1992

Endothelial leukocyte adhesion molecule-1-dependent adhesion of colon carcinoma cells to vascular endothelium is inhibited by an antibody to Lewis fucosylated type I carbohydrate chain.

Endothelial leukocyte adhesion molecule-1 (ELAM-1) has been determined to be the mediator of adhesion of colon carcinoma cells to interleukin-1 (IL-1)-activated endothelial cells. To identify ELAM-1 ligand in colon carcinoma cells, we have screened a series of 11 monoclonal antibodies directed to these cells and found that only one MBr8 was able to inhibit the IL-1-induced increment in adhesion of HT29 and of SW948 colon carcinoma lines to endothelial cells. In contrast, MBr8 did not bind to polymorphonuclear cells, monocytes, and lymphocytes and did not inhibit polymorphonuclear adhesion to IL-1-activated endothelial cells. As expected, an ELAM-1 monoclonal antibody strongly inhibited IL-1 induced increment of adhesion of HT29, SW948, and polymorphonuclear cells. As negative control, MG63 osteosarcoma cells were used. These cells adhere more efficiently to IL-1 activated endothelial cells but MBr8 and ELAM-1 monoclonal antibodies did not affect their adhesion. The effect of MBr8 was also tested in an experimental system in vivo. As described previously, radiolabeled HT29 cell retention in the lung of nude mice was increased in animals given IL-1. MBr8 administration to nude mice or pretreatment of tumor cells with it inhibited this effect. These data suggest that cell adhesion to ELAM-1 might be mediated by different, cell type specific, sugar ligands.

Antibodies, Monoclonal↗

PubMed1995

Conformational changes in adhesive proteins modulate their adhesive function.

A large family of glycoproteins mediates cell adhesion by binding to cellular receptors. As a group, these adhesive proteins are large in size, multi-domainal in composition, and are capable of self-association. A general property of the adhesive proteins is their susceptibility to structural modulation, and conformational change provides a mechanism for regulation of their adhesive functions. To illustrate this concept, conformational alterations of thrombospondin, fibrinogen and fibronectin are shown to modulate their adhesive potential. Thus, conformational status of the adhesive proteins contributes to the regulation of cell adhesion.

Cell Adhesion↗

PubMed1995

Melanoma cell spreading on fibronectin induced by 12(S)-HETE involves both protein kinase C- and protein tyrosine kinase-dependent focal adhesion formation and tyrosine phosphorylation of focal adhesion kinase (pp125FAK).

Our previous work demonstrated that 12(S)-HETE, a lipoxygenase metabolite of arachidonic acid, promoted B16 amelanotic melanoma (B16a) cell spreading on fibronectin. In the current study, we investigated the biochemical mechanisms of the 12(S)-HETE induced response. 12(S)-HETE treatment resulted in a time-dependent increase in B16a cell spreading on fibronectin, which was blocked by either calphostin C or by genistein but not by H8. Two hours following cell plating, both spontaneous and 12(S)-HETE promoted cell spreading reached their maximum (nearly 100%). Spontaneous cell spreading was inhibited by the select 12-lipoxygenase inhibitor, BHPP, whose inhibitory effect could be overcome by increasing doses of exogenous 12(S)-HETE. 12(S)-HETE-treated B16a cells plated on either fibronectin or cultured on their own extracellular matrix demonstrated increased vinculin and tyrosine-phosphorylated proteins, which were colocalized at focal adhesions. The increase in vinculin localization to focal adhesions appeared to be a post-transcriptional process, since 12(S)-HETE treatment did not alter the overall protein level of vinculin in tumor cells, but resulted in a specific enrichment of vinculin to focal adhesions. Pretreatment of B16a cells with either calphostin C or genistein abolished 12(S)-HETE-increased formation of vinculin- and phosphotyrosine-containing focal adhesions. Immunoblotting using antiphosphotyrosine antibody 4G10 demonstrated, following 12(S)-HETE stimulation, an increased tyrosine phosphorylation of several proteins in focal adhesions; most prominently, a approximately 155 kd protein, a 120-130 kd protein cluster, a 76 kd protein, and a 42/44 kd complex. Immunoprecipitation with anti-phosphotyrosine antibody PY20 revealed increased tyrosine phosphorylation, post 12(S)-HETE stimulation, of proteins migrating at 120, 76, and 42/44 kd, of which the 120 kd protein co-migrated with pp125FAK. Immunoprecipitation with anti-FAK antibody BC-3 followed by immunoblotting with anti-phosphotyrosine antibody RC20H demonstrated a time-dependent hyperphosphorylation of pp125FAK. The present study suggests that 12(S)-HETE promoted melanoma cell spreading on fibronectin involves tyrosine phosphorylation of pp125FAK and protein kinase C- and tyrosine kinase-dependent focal adhesion formation.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

PubMed1998

Adhesion to fibronectin's EDb domain induces tyrosine phosphorylation of focal adhesion proteins in Balb/c 3T3 cells.

Balb/c 3T3 cell adhesion on substrata coated with fibronectin's (FN) alternatively-spliced EDb, implicated in some tumor cell systems, and its neighboring type III repeats (III7 and III8) induced intracellular signaling coincident with morphological responses. These events were analysed using minigene-expressed proteins containing various permutations of type III repeats of FN. Cells adherent to the tri-repeat protein 7-EDb-8 were compared to those attached to the tri-repeat 8-9-10 which can interact with integrins through RGD and its synergistic sequences. Cell adhesion to 7-EDb-8 generated rapid tyrosine phosphorylation of several intracellular proteins (particularly the complex at 120-130 kD), with the overall phosphorylation level and its sensitivity to tyrosine kinase inhibitors similar to responses on the 8-9-10 tri-repeat. This similarity contrasted with the differential morphological responses of cells mediated by these proteins. Further analysis of the kinetics of phosphorylation through immunoblotting of two focal adhesion proteins, p125FAK and pl30cas, revealed a profile for Balb/c 3T3 adhesion to 7-EDb-8 distinct from that on 8-9-10. EDb mono-repeat was also more potent for inducing both limited cell spreading and FAK tyrosine phosphorylation than its neighboring repeats III7 or III8. Examination of cellular localization of FAK and vinculin showed that cells spread on the 7-EDb-8 substratum displayed vinculin-positive focal complex-like structures at the cell periphery, in contrast to the classical focal adhesions seen in 8-9-10-adherent cells. These results suggest that EDb induces cell signaling events, leading to tyrosine phosphorylation of focal adhesion proteins, through a mechanism different from that mediated by integrins recognizing sequences in III8-9-10. EDb-dependent signaling may have special significance in some tumor systems.

3T3 Cells↗

PubMed1993

Identification of sequences required for the efficient localization of the focal adhesion kinase, pp125FAK, to cellular focal adhesions.

The integrin family of heterodimeric cell surface receptors play critical roles in multiple biological processes by mediating cellular adhesion to the extracellular matrix (ECM). Adhesion triggers intracellular signaling cascades, including tyrosine phosphorylation and elevation of [Ca2+]i. The Focal Adhesion Kinase (FAK or pp125FAK), a protein tyrosine kinase that colocalizes with integrins in cellular focal adhesions, is a prime candidate for a mediator of integrin signaling events. Here we report an analysis of the domain structure of FAK in which we have identified a contiguous stretch of 159 amino acids within the COOH terminus essential for correct subcellular localization. When placed in the context of an unrelated cytosolic protein, this Focal Adhesion Targeting (FAT) sequence functions to efficiently mediate the focal adhesion localization of this fusion protein. Furthermore, this analysis suggests that pp125FAK cannot be activated oncogenically by mutation. This result could be explained if pp125FK either exhibits a narrow substrate specificity or is diametrically opposed by cellular phosphatases or other cellular processes.

Amino Acid Sequence↗

PubMed2001

Stimulation of beta1 integrin down-regulates ICAM-1 expression and ICAM-1-dependent adhesion of lung cancer cells through focal adhesion kinase.

Adhesion molecules are involved in intracellular signaling in various physiological and pathological processes including metastasis and growth of tumor cells. Tumor cells interact with various host cells as well as with extracellular matrices through certain adhesion molecules such as integrins. We here propose that stimulation of beta1 integrin reduces intercellular adhesion molecule (ICAM)-1-mediated interaction of lung cancer cells with CTLs. This concept is based on the following findings: (a) engagement of beta1 integrins on certain lung cancer cells by a specific antibody or by ligand matrices such as fibronectin and collagen markedly reduced ICAM-1 expression on the cell surface and induced sICAM-1; (b) down-regulation of ICAM-1 by stimulation of beta1 integrins was abrogated by tyrosine kinase inhibitors or by transfection of dominant negative truncations of focal adhesion kinase (FAK); (c) engagement of beta1 integrins also reduced ICAM-1-dependent adhesion of lung cancer cells to T cells, a process completely inhibited by tyrosine kinase inhibitors and by transfection of dominant negative forms of FAK; and (d) stimulation of beta1 integrins prevented killing of lung cancer cells by autologous CTLs. In malignant tumors, cancer cells, including lung cancer cells, are surrounded by extracellular matrix proteins such as fibronectin and collagen. This suggests that the engagement of beta1 integrins by matrix proteins potentially occurs in cancer cells in vivo and that continuous stimulation via beta1 integrins reduces ICAM-1-expression, ICAM-1-mediated adhesion of cancer cells to CTLs and their killing by CTLs. Our results suggest that such processes can lead to the escape of lung cancer cells in vivo from immunological surveillance.

Antibodies, Monoclonal↗

PubMed1997

Bone marrow fibroblast exposure to the inflammatory cytokines tumor necrosis factor-alpha and interferon-gamma increases adhesion of acute myeloid leukemia cells and alters the adhesive mechanism.

Human acute myeloid leukemia (AML) cells adhere to bone marrow fibroblasts (BMF) and extracellular matrix proteins including fibronectin. Adhesion is increased when fibroblast monolayers are exposed to tumor necrosis factor-alpha (TNF) alone and in combination with interferon-gamma (IFN) or interleukin-4 (IL-4). The combination of TNF and IFN caused enhanced AML cell adhesion to treated BMFs, from a mean of 25.0 +/- 4.1% to 36.3 +/- 5.4% (p = 0.0007). Enhanced binding was partially a result of upregulated vascular cell adhesion molecule-1 expression on BMFs. Intercellular adhesion molecule-1 was also upregulated, but did not appear to play a role in the increased binding to cytokine-stimulated BMFs. In contrast to observed adhesion to resting BMFs, AML cells binding to TNF/IFN-stimulated BMFs rely more heavily on the VLA-4 alpha chain (CD49d). In some cases, alpha4 integrin chain antibody was more effective than beta1 antibody in blocking binding, suggesting that a non-beta1 alpha4 integrin, possibly alpha4 beta7, on AML cells may act as a stromal ligand. The addition of alpha4 antibody to beta1 and beta2 antibodies significantly increased the inhibition of AML cells to stimulated BMFs. The myeloid cytokines granulocyte colony stimulating factor, granulocyte-monocyte colony stimulating factor, interleukin-3 and stem cell factor enhanced the adhesion of AML blast cells to BMFs in some cases. The phorbol ester PMA, however, consistently upregulated AML cell-binding to BMFs, the increase being mediated entirely via beta1 and beta2 integrins without altering AML cell integrin expression. Binding of AML cells to marrow stroma can be enhanced by influences on leukemic cell or stroma. Enhanced binding under these conditions occurs via different pathways, illustrating the heterogeneity of mechanisms underlying leukemic cell retention within the bone marrow stroma.

Acute Disease↗

PubMed1991

Lectin cell adhesion molecules (LEC-CAMs): a new family of cell adhesion proteins involved with inflammation.

The means by which leukocytes, including lymphocytes, monocytes, and neutrophils, migrate from the circulation to sites of acute and chronic inflammation is an area of intense research interest. Although a number of soluble mediators of these important cellular interactions have been identified, a major site of great importance to the inflammatory response is the physical interface between the white cell and the endothelium. This critical association is mediated by an array of cell surface adhesion molecules. Previous data have demonstrated that the integrin subfamily of heterotypic adhesion molecules was a major component of these adhesive interactions, although it was clear that other, non-integrin-like molecules of unknown identity also seemed to be involved during the inflammatory process. A number of these other cell-surface glycoproteins which may be involved with inflammation have recently been characterized by molecular cloning. These glycoproteins, including the peripheral lymph node homing receptor (pln HR), the endothelial cell adhesion molecule (ELAM), and PADGEM/gmp140, are all members of a family of proteins which are unified by the inclusion of three characteristic protein motifs: a lectin or carbohydrate recognition domain, an epidermal growth factor (egf) domain, and a variable number of short consensus repeats (scr) which are also found in members of the complement regulatory proteins. The appearance of lectin domains in all of these adhesion molecules is consistent with the possibility that these glycoproteins function by binding to carbohydrates which are expressed in a cell and/or region specific manner, and the members of this adhesion family have been given the generic name LEC-CAM (lectin cell adhesion molecules).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1996

Novel animal model for studying the molecular mechanisms of bacterial adhesion to bone-implanted metallic devices: role of fibronectin in Staphylococcus aureus adhesion.

Infection around metallic implants is a rare but severe complication of orthopaedic surgery. A novel animal model mimicking conditions of internal fixation devices was developed to evaluate the role of host proteins adsorbed on metallic devices in promoting adhesion and colonization of the material surfaces by Staphylococcus aureus. Small plates made of pure titanium were either fixed (three screws per plate) onto the iliac bones of guinea pigs or implanted into their subcutaneous space as controls. Five to 6 weeks after surgery, the plates and screws were removed from the previously killed animals, carefully rinsed in buffer, and tested in an in vitro assay of S. aureus adhesion to metallic surfaces. To evaluate the role of fibronectin in staphylococcal adhesion to explanted plates and screws, a mutant of S. aureus that is specifically defictive in fibronectin adhesion due to decreased expression of the fibronectin adhesin was compared with its isogenic parental strain. A significant reduction in adhesion of the fibronectin adhesin-defective mutant compared with the parental strain occurred on both the subcutaneously implanted and bone-implanted metallic plates. The results of this specific biological assay suggest that fibronectin is present on bone-implanted metallic devices and promotes attachment of S. aureus to their surfaces. This novel experimental model should help, to characterize several parameters of bacterial adhesion to metallic orthopaedic devices and to develop novel anti-adhesive strategies for preventing such infections.

Animals↗