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At least 739 records · Page 41Linked to original sources
PubMed1995

Calcium-dependent homotypic adhesion through leukocyte function-associated antigen-1/intracellular adhesion molecule-1 induces interleukin-1 and parathyroid hormone-related protein production on adult T-cell leukemia cells in vitro.

Adult T-cell leukemia (ATL) is a human T-cell leukemia virus type I (HTLV-I)-infected lymphoproliferative disorder that shows a characteristic nodular infiltration into various tissues, hypercalcemia, and subsequent rapid increase of peripheral ATL cell number. ATL cells and HTLV-I-infected T-cell lines also make cluster formation rapidly after the non-stimulative culture. However, the mechanism of the acute proliferation of ATL cells remains to be understood. We report the following novel features of homotypic adhesion via leukocyte function-associated antigen-1 (LFA-1)/intracellular adhesion molecule-1 (ICAM-1) pathway that suggest a role for it in cytokine production and rapid proliferation of ATL cells: (1) ATL cells show clustering in a calcium dependent manner, even at the higher concentration; (2) ATL cells consistently and highly express ICAM-1 and an active form of LFA-1, whereas integrin expression, except for LFA-1, is rather lower compared with that of normal CD4+ T cells; (3) ATL cells make conjugate formation within 6 minutes and clustering within 48 hours, both of which are inhibited by the addition of monoclonal antibodies (MoAbs) against LFA-1 and ICAM-1; (4) spontaneous mRNA transcription and protein secretion of both interleukin-1 and parathyroid hormone-related protein are observed consistently in ATL cells, and these productions are inhibited by anti-LFA-1 and anti-ICAM-1 MoAbs but are markedly increased by cross-linking of LFA-1 and ICAM-1 by the immobilized specific MoAbs; and (5) proliferative responses of ATL cells are also inhibited by these MoAbs. We propose that ATL cells proliferate in sequential events: the homotypic and calcium-dependent adhesion through LFA-1/ICAM-1, the signal transduction through these adhesion molecules, the production of cytokines, and the proliferation.

Bone Resorption↗
PubMed1993

Several extracellular domains of the neural cell adhesion molecule L1 are involved in neurite outgrowth and cell body adhesion.

The neural cell adhesion molecule L1 is a multidomain protein that plays important roles in cell adhesion, migration, and neurite outgrowth. To analyze structure-function relationships of L1 in neurite outgrowth and cell body adhesion, we have expressed and purified a set of different fragments of the extracellular part of this glycoprotein in CHO cells and in Escherichia coli. When neurite outgrowth from small cerebellar neurons was measured on substrate-coated L1 or L1 fragments, neurite outgrowth was promoted by the immunoglobulin-like domains I-II, III-IV, and V-VI, and by the fibronectin type III homologous repeats 1-2, while the fibronectin type III homologous repeats 3-5 were ineffective. In contrast, cell bodies of small cerebellar neurons adhered mostly to the immunoglobulin-like domains I-II and V-VI, and to the fibronectin type III homologous repeats 3-5, but less to the immunoglobulin-like domains III-IV and fibronectin type III homologous repeats 1-2. In both assays, the neuronal cell surface receptor for all active protein fragments was identified as L1. No significant differences in functional activities were found between fragments with and without carbohydrate structures. These findings indicate that L1 uses several domains for homophilic interactions overlapping for the two functions analyzed here, but also showing some regional specialization. Furthermore, we show that a homophilic molecule uses several domains in one function, with neurite outgrowth requiring more domains than adhesion for maximal activity.

Animals↗
PubMed1998

Platelet/endothelial cell adhesion molecule-1 serves as a costimulatory agonist receptor that modulates integrin-dependent adhesion and aggregation of human platelets.

Platelet/endothelial cell adhesion molecule-1 (PECAM-1) is a 130-kD member of the Ig gene superfamily that is expressed on the surface of circulating platelets, monocytes, neutrophils, and selective T-cell subsets. It is also a major component of the endothelial cell intercellular junction. Previous studies have shown that cross-linking PECAM-1 on the surface of leukocytes results in the activation of adhesion molecules of both the beta 1 and beta 2 integrin family. In addition, the process of leukocyte transendothelial migration appears to be mediated, at least in part, by homophilic adhesive interactions that take place between leukocyte and endothelial cell junctional PECAM-1 molecules. However, little is known about the functional role of this membrane glycoprotein in human platelets. In the present study, we examined the effects of PECAM-1 engagement on integrin-mediated platelet-extracellular matrix or platelet-platelet interactions. Bivalent, but not monovalent, anti-PECAM-1 monoclonal antibodies (MoAbs) specific for membrane-proximal Ig-homology domain 6 significantly augmented platelet deposition (increased surface coverage) and aggregation (increased average size) onto extracellular matrix, under both oscillatory or defined low shear flow conditions (200 s-1) in a modified cone and plate viscometer. Moreover, bivalent anti-domain 6 MoAbs were capable of serving as costimulatory agonists to markedly enhance both adenosine diphosphate (ADP)- and platelet activating factor (PAF)-induced platelet aggregation resonses. These antibodies appeared to act via outside-in signal transduction through PECAM-1, as evidenced by the fact that their binding (1) led to conformational changes in the alpha IIb beta 3 integrin complex, (2) induced surface expression of P-selectin, and (3) resulted in the tyrosine phosphorylation of PECAM-1. Together, these data support a role for PECAM-1 in cellular activation and suggest that PECAM-1 may serve as a costimulatory agonist receptor capable of modulating integrin function in human platelets during adhesion and aggregation.

Blood Platelets↗
PubMed1998

MEMD, a new cell adhesion molecule in metastasizing human melanoma cell lines, is identical to ALCAM (activated leukocyte cell adhesion molecule).

From a differential mRNA display comparing a non- and a highly metastasizing human melanoma cell line, we isolated and characterized memD. memD is preferentially expressed in the highly metastasizing melanoma cell lines of a larger panel. The encoded protein, MEMD, is identical to activated leukocyte cell adhesion molecule (ALCAM), a recently identified ligand of CD6. ALCAM is involved in homophylic (ALCAM-ALCAM) and heterophylic (ALCAM-CD6) cell adhesion interactions. We have studied MEMD/ALCAM cell-cell interactions between human melanoma cells. The expression of this cell adhesion molecule not only correlates with enhanced metastatic properties and with aggregational behavior of human melanoma cells as tested by FACS analysis, but transfection experiments also make clear that MEMD/ALCAM expression is essential for cell-cell interaction of the investigated human melanoma cells. As the melanoma cell lines analyzed are all CD6 negative, these results strongly suggest that MEMD/ALCAM is an adhesion molecule mediating homophylic clustering of melanoma cells. MEMD/ALCAM expression is not restricted to subsets of leukocytes and melanoma cells, it can also be found in healthy organs and in several other malignant tumor cell lines. Besides, MEMD/ALCAM is also expressed in cultured endothelial cells, pericytes and melanocytes, in xenografts derived from the radial and vertical growth phase and in 4 of 13 melanoma metastasis lesions. The potential role is discussed of MEMD/ALCAM mediated cell-cell interactions in migration of mobile cells (ie, activated leukocytes, metastasizing tumor cells) through tissues.

Activated-Leukocyte Cell Adhesion Molecule↗
PubMed1999

Requirement for focal adhesion kinase in tumor cell adhesion.

Focal adhesion kinase (FAK) is a nonreceptor protein tyrosine kinase and a major phosphotyrosine-containing protein. FAK is found in cell-matrix attachment sites (focal adhesions), and is activated on integrin-ligand binding and by other signaling pathways. Several roles have been proposed for FAK; here we report a novel function. We observed abundant FAK protein in all human melanoma cell lines tested except COLO839, a line that grows predominantly in suspension and was derived from peripheral blood. Five adherent lines, isolated from solid metastases in the same patient as COLO839, did express FAK. We derived four adherent sublines from COLO839. These did express FAK, even when plated on bacteriological plastic, to which they did not adhere. Thus, substrate attachment was not required for FAK expression. Three of the adherent sublines were then grown in the presence of antisense oligonucleotides to the initial FAK coding sequence. All showed substantially reduced FAK expression and, interestingly, the cells largely detached from the substrate while continuing to grow. Similar results were obtained with an independent melanoma line, DX3. Thus, FAK expression appears to be required by melanoma cells for substrate adhesion.

Base Sequence↗
PubMed1999

Astrocytoma adhesion to extracellular matrix: functional significance of integrin and focal adhesion kinase expression.

Evidence is accumulating implicating a role for integrins in the pathogenesis of cancer, a disease in which alterations in cellular growth, differentiation, and adhesive characteristics are defining features. In the present report we studied a panel of 8 human astrocytoma cell lines for their expression of integrin subunits by RT-PCR, and of integrin heterodimers by immunoprecipitation analyses. The functionality of integrin heterodimers was assessed using cell attachment assays to plastic or single matrix substrates. Downstream effects of integrin activation were studied by western blot analyses of FAK expression in human astrocytoma cell lines growing on plastic and on a fibronectin matrix, and in 13 primary human brain tumor specimens of varying histopathological grade. Furthermore, we studied tyrosine phosphorylation of FAK in astrocytoma cells growing on plastic versus fibronectin. Finally, we analyzed the effects of intermediate filament gene transfer on FAK phosphorylation in SF-126 astrocytoma cells. Our data show that astrocytoma cell lines express various integrin subunits by RT-PCR, and heterodimers by immunoprecipitation analyses. The beta1 and alphav integrin subunits were expressed by all astrocytoma cell lines. The alpha3 subunit was expressed by all cell lines except SF-188. By immunoprecipitation, the fibronectin receptor (alpha5beta1 integrin heterodimer) and the vitronectin receptor (alphavbeta3) were identified in several cell lines. Astrocytoma cell attachment studies to human matrix proteins suggested that these integrin heterodimers were functional. Using confocal laser microscopy, we showed that FAK was colocalized to actin stress fibers at sites of focal adhesion complexes. By western blot, FAK was variably but quite ubiquitously expressed in human astrocytoma cell lines, and in several primary human astrocytoma specimens. When U373 and U87 MG astrocytoma cells bind to a fibronectin matrix, FAK is phosphorylated. GFAP-transfected SF-126 human astrocytoma cells were shown to overexpress the phosphorylated form of FAK only when these cells were placed on a fibronectin matrix. This result is of interest because it suggests that manipulations of the astrocytoma cytoskeleton per se can bring about potential signaling changes that channel through integrins and focal adhesion sites leading to activation of key kinases such as FAK.

Adult↗
PubMed1994

Regulation of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in human vascular smooth muscle cells.

Vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin are inducible proteins involved in cell-cell adhesion. Immunohistochemical studies have indicated that human atherosclerotic plaques contain smooth muscle cells (SMCs) that express ICAM-1 and VCAM-1. Recently, we demonstrated that SMCs in culture express a functionally active cytokine-inducible ICAM-1. SMCs and mononuclear cells participate in the local accumulation of cytokines and related growth factors in atherosclerotic lesions. Therefore, we determined the effects of different cytokines and growth factors on mRNA content and cell surface expression of VCAM-1, ICAM-1, and E-selectin in cultured human aortic SMCs by Northern blotting, quantitative polymerase chain reaction amplification, and immunofluorescence flow cytometry. Under basal conditions of cultivation, both VCAM-1 mRNA and membrane expression of VCAM-1 were low and were induced very little by interleukin-1 beta (100 U/mL). Platelet-derived growth factor or transforming growth factor-beta decreased VCAM-1 mRNA basal expression. Treatment of SMCs with tumor necrosis factor-alpha (TNF-alpha) led to an increase in both VCAM-1 mRNA and cell surface expression for VCAM-1 in a dose- and time-dependent manner. Interferon-gamma induced a weak increase in VCAM-1 mRNA expression, with no synergistic effect on the stimulation by TNF-alpha. Various differences were noted between the expression of ICAM-1 and VCAM-1 genes, because interleukin-1 beta induced substantial amounts of ICAM-1 but not VCAM-1. The addition of interferon-gamma delays the time at which peak expression of ICAM-1 in response to TNF-alpha stimulation occurs. Under our conditions, we did not detect any expression of E-selectin by SMCs. These results suggest that cytokines regulate VCAM-1 and ICAM-1 expression on arterial SMCs and could play an important role in the pathophysiology of inflammatory and immune processes in atherosclerosis.

Base Sequence↗
PubMed1996

Regulation and activation of focal adhesion kinase and paxillin during the adhesion, proliferation, and differentiation of prostatic epithelial cells in vitro and in vivo.

Focal adhesion kinase (pp125FAK) is a nonreceptor protein tyrosine kinase transducing signals initiated through integrin activation triggered by cell/extracellular matrix (ECM) interactions. To examine its role in epithelial cell adhesion, proliferation, and differentiation, we have studied pp125FAK expression, activity, and association with paxillin in two canine prostate models in which these functions can be selectively regulated: in vitro by vitronectin (VN) and serum factors, and in vivo by sex steroids. Kinetic studies revealed that the adhesion and spreading of prostatic epithelial cells in primary culture was regulated by serum VN and a natural ECM containing VN produced by prostate cells. While barely detectable in freshly isolated prostate cells, proliferating cells, after 72 h in culture, expressed higher levels of FAK mRNA (8-fold), pp125FAK (50-fold), and paxillin (50-fold). In prostate cells with a reduced growth rate after 2 weeks in culture, we observed a decrease in pp125FAK (4-fold) and its transcript (3-fold), but no change in paxillin. In vivo, both proteins were undetectable in normal and hyperplastic glands composed of a well differentiated epithelium, and in prostates restored by androgen supplementation. In contrast, pp125FAK and paxillin were up-regulated by androgen deprivation (castration) and further increased by estrogen treatment, which yielded metaplastic prostates mostly composed of proliferating basal epithelial cells. Moreover, both proteins were constitutively phosphorylated on tyrosine in the metaplastic prostate, as well as in proliferating cultured cells. Together, these results demonstrate that pp125FAK expression is regulated at the protein and mRNA levels and forms active signaling complexes with paxillin when epithelial cells in contact with ECM proteins are induced to proliferate in vivo and in vitro.

Amino Acid Sequence↗
PubMed1999

Adhesion of human monocytic THP-1 cells to endothelial cell adhesion molecules or extracellular matrix proteins via beta1 integrins regulates heparin binding epidermal growth factor-like growth factor (HB-EGF) expression.

Adherence to endothelium and then to the extracellular matrix is a prerequisite for extravasation of monocytes into injured tissues. There, monocytes differentiate into macrophages and express heparin binding epidermal growth factor-like growth factor (HB-EGF), a key growth factor involved in normal wound healing. We investigated whether the interaction of human monocytic THP-1 cells with the endothelial cell adhesion molecules (vascular CAM-1, VCAM-1; intercellular adhesion molecule-1 ICAM-1 and endothelial-selectin, E-selectin), or the extracellular matrix (ECM) proteins (fibronectin, FN; laminin, LN and fibrinogen, FG) regulate HB-EGF expression. We have shown that adherence of THP-1 cells via VCAM-1, E-selectin or FN, which are all overexpressed at sites of inflammation, potentiates HB-EGF mRNA expression. In contrast, adhesion of THP-1 cells via ICAM-1 or FG, has no significant effect. Since THP-1 cells interact with ICAM-1 and FG through beta2 integrins, and with VCAM-1 and FN via beta1 integrins, regulation of HB-EGF expression appears to be specific to beta1 integrin ligation. In addition, we demonstrate that THP-1 binding to LN, through the beta1 integrin VLA-6, down regulates HB-EGF expression. Thus physiologically, transient destruction of LN and expression of VCAM-1, E-selectin and fibronectin at sites of inflammation, may locally induce HB-EGF overexpression.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1996

Glycosylphosphatidylinositol toxin of Plasmodium up-regulates intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin expression in vascular endothelial cells and increases leukocyte and parasite cytoadherence via tyrosine kinase-dependent signal transduction.

In this study we demonstrate that glycosylphosphatidylinositol (GPI) of malaria parasite origin directly increases cell adhesion molecule expression in purified HUVECs in a dose- and time-dependent manner, resulting in a marked increase in parasite and leukocyte cytoadherence to these target cells. The structurally related glycolipids dipalmitoyl-phosphatidylinositol and iM4 glycoinositolphospholipid of Leishmania mexicana had no such activity. Malarial GPI exerts this effect by activation of an endogenous GPI-based signal transduction pathway in endothelial cells. GPI induces rapid onset tyrosine phosphorylation of multiple intracellular substrates within 1 min of addition to cells in a dose-dependent manner. This activity can be blocked by the protein tyrosine kinase-specific antagonist herbimycin A, genistein, and tyrphostin. These tyrosine kinase antagonists also inhibit GPI-mediated up-regulation of adhesion expression and parasite cytoadherence. GPI-induced up-regulation of adhesion expression and parasite cytoadherence can also be blocked by the NF kappa B/c-rel antagonist pyrrolidine-dithiocarbamate, suggesting the involvement of this family of transcription factors in GPI-induced adhesin expression. The direct activation of endothelial cells by GPI does not require the participation of TNF or IL-1. However, GPI is also responsible for the indirect pathway of increased adhesin expression mediated by TNF and IL-1 output from monocytes/macrophages. Total parasite extracts also up-regulate adhesin expression and parasite cytoadherence in HUVECs, and this activity is blocked by a neutralizing mAb to malaria GPI, suggesting that GPI is the dominant agent of parasite origin responsible for this activity. Thus, a parasite-derived GPI toxin activates vascular endothelial cells by tyrosine kinase-mediated signal transduction, leading to NF kappa B/c-rel activation and downstream expression of adhesins, events that may play a central role in the etiology of cerebral malaria.

Animals↗
PubMed1998

The COOH-terminal domain of the focal adhesion kinase induces loss of adhesion and cell death in human tumor cells.

Focal adhesion kinase (FAK) is a tyrosine kinase that is linked to signaling pathways between cells and their extracellular matrix. An alternate transcript of the COOH-terminal region of the FAK gene, called FAK-related nonkinase, has been shown to act as an inhibitor of FAK in chicken embryo fibroblasts. We have designed an analogous segment of human FAK, FAK COOH-terminal domain (FAK-CD), and transfected this construct into human tumor cells. Expression of FAK-CD inhibited cell growth in BT474 human breast cancer cells and C8161 human melanoma cells. To characterize the nature of growth inhibition, we developed an inducible system of FAK-CD expression and demonstrated that the induced FAK-CD protein localized to focal adhesions, causing cellular rounding, an irreversible loss of adhesion, and subsequent cell death. In addition, expression of FAK-CD reduced tyrosine phosphorylation of FAK, suggesting that FAK-CD may be a potent inhibitor of FAK in human tumor cells.

Alternative Splicing↗
PubMed2000

Two different types of nonthrombogenic surfaces: PEG suppresses platelet adhesion ATP-independently but HEMA-St block copolymer requires ATP consumption of platelets to prevent adhesion.

Poly(ethylene glycol) (PEG) and a hydrophobic-hydrophilic microdomain structured block copolymer comprising poly(2-hydroxyethyl methacrylate) and polystyrene (HEMA-St) have been reported to show good blood compatibility owing to inhibition of platelet activation. By using a computer-assisted novel technique to analyze platelet behavior on the surfaces, we found two different mechanisms to prevent platelet adhesion. Platelets were prevented from adhesion and spreading on the microdomain surface and retained cell movement for a long time. The platelet movement velocity was not significantly different between PEG-grafted surfaces and HEMA-St block copolymer-cast surfaces. However, platelet motion was qualitatively different. Platelets on HEMA-St block copolymer-cast surfaces moved with rolling, spinning, and vibrating, whereas platelet movement was limited to oscillatory vibration on PEG-grafted surfaces. When platelets were treated with NaN(3), an adenosine triphosphate (ATP) synthesis inhibitor, before contacting the surfaces, platelets movement velocity was decreased only on HEMA-St block copolymer-cast surfaces. Such an inhibitory effect was hardly observed with platelets on PEG-grafted surfaces. We propose two different mechanisms to prevent platelet adhesion onto surfaces. One is ATP-independent as observed with PEG, and the other is ATP-dependent for HEMA-St block copolymer, where platelets consume ATP to prevent adhesion.

Adenosine Triphosphate↗
PubMed1974

Adhesion of synthetic organic polymer on soft tissue. I. A fast setting polyurethane adhesive.

Conventional polyurethane prepolymers have been shown to adhere to living biological tissues. However, their setting is not sufficiently expedient to permit convenient applications in vivo. A prepolymer prepared from the highly reactive 6-chloro-2,4,5-trifluoro-1,3-phenylene diisocyanate, castor oil, and a trace of pyridine has afforded an adhesive which sets in about 2 min in vivo. The fast setting has resulted in poor adhesion on biological tissue. The bonding has been improved by the inclusion of tolylene diisocyanate in the composition without affecting the fast curing rate of the prepolymer. The dispersion of the adhesive and its cohesion after solidification have been adjusted by other minor additives. Preliminary evaluation on animals indicates that this adhesive is most useful as a hemostatic coating in hepatic lacerations.

Animals↗
PubMed1990

Adsorption of plasma proteins and adhesion of platelets onto novel polyetherurethaneureas--relationship between denaturation of adsorbed proteins and platelet adhesion.

Novel polyetherurethaneureas which have been synthesized by the present authors were chosen for the substrate polymers, on which adhesion of platelets was investigated. The number of adhered platelets and the amount of serotonin released from platelets adhered on the polymers and the protein-coated polymers were determined by radioisotope method. Both of them were enhanced with increasing content of urea linkages in the polyetherurethaneureas. The platelet adhesion was discussed in terms of the denaturation of plasma proteins upon adsorption, which was determined by Fourier-transform infrared spectroscopy. With increasing degree of protein denaturation, the platelet adhesion and the serotonin release were enhanced. This relationship was particularly evident in the case of albumin adsorption. It was shown that the surface properties of substrate polymers affect the protein adsorption, which in turn influences the adhesion of platelets.

Adsorption↗
PubMed1977

Studies on intercellular adhesion. I. Adhesion of neural retina cells to isotypic aggregates in serum free medium.

A quantitative assay for intercellular adhesion, which is a modification of the collecting aggregate assay (Roth et al., '71) is described. The use of mechanically dissociated single cells labeled with 3H-leucine, and of a gyratory shaker increased considerably the efficiency of cell collection. With chick embryo neural retina, it was shown that isotypic cell adhesion occurs in simple synthetic media and even in sodium chloride solution suggesting that divalent cations do not play a major role in adhesion of these cells. Cell collection in media without serum was not affected by metabolic or protein synthesis inhibitors. However, cell adhesion was temperature-dependent since no collection occurred at 4 degrees C but was maximal at 38 degrees C.

Azides↗
PubMed1985

cAMP-induced phenotypic reversion of adhesion, aggregation, and endocytosis in adhesion-defective CHO cell variants.

ADvF11 cells are a CHO adhesion variant which, unlike wild type (WT) cells, are not able to adhere to fibronectin (Fn) coated substrata or to be aggregated by Fn-beads. However, ADvF11 cells bind Fn-beads to the same extent as WT cells, thus suggesting that the defect(s) associated with ADvF11 cells are distal to the initial receptor-ligand binding event (Cheung and Juliano, Exp. Cell Res. 152:127, 1984). In this communication we report that cAMP analogs such as dibutyryl-cAMP (dbcAMP) and 8-bromo-cAMP are able to correct defect(s) associated with ADvF11 cells enabling them to adhere to Fn-coated dishes and to aggregate in the presence of Fn-beads. However, only approximately 40% of ADvF11 cells were found to be responsive to dbcAMP suggesting heterogeneity in the cell population with respect to dbcAMP sensitivity. Further analysis of this partial response led us to isolate a subclone of ADvF11 cells, F11CA11, which is highly responsive to dbcAMP treatment. Induction of Fn-mediated cell adhesion and aggregation in F11CA11 by dbcAMP is both time and dose dependent. Optimal responses were obtained after overnight incubation in alpha-MEM containing, 1% fetal calf serum, 4% bovine serum albumin, 0.5 mM dbcAMP and 0.2 mM methyl-isobutyl-xanthine (MIX), a phosphodiesterase inhibitor. Under these conditions, 70-80% of F11CA11 cells were found to be adherent, compared to 5-7% of untreated F11CA11 cells and 95-100% of WT cells. Aggregation of dbcAMP-MIX treated F11CA11 cells induced by Fn-beads also approached that of WT cells. In addition, treatment with dbcAMP-MIX markedly increased the ability of F11CA11 cells to internalize Fn-beads. The maintenance of the adherent phenotype required the constant presence of dbcAMP-MIX. Removal of dbcAMP-MIX from the incubation medium resulted in return to the original nonadhesive phenotype. Thus, elevation of cAMP levels can dramatically modify the behavior of F11CA11 cells with respect to fibronectin mediated adhesion, aggregation and endocytosis, in effect causing a phenotypic reversion of all three parameters to wild type status. This suggests that the mechanisms for adhesion, aggregation and endocytosis may each involve regulation by cyclic AMP-protein kinase systems.

1-Methyl-3-isobutylxanthine↗
PubMed1999

Influenza A virus up-regulates neutrophil adhesion molecules and adhesion to biological surfaces.

Influenza A virus (IAV) binds to sialylated neutrophil surface components (e.g., CD43 and sialyl Lewisx antigen) and induces both activation and functional depression of neutrophils. We report that IAV enhanced neutrophil adhesion to surfaces coated with serum or serum components, but not to uncoated plastic. IAV up-regulated expression of integrins (CD11b and CD11c) and carcinoembryonic-related antigens on neutrophils, while reducing expression of CD43, L-selectin, and P-selectin glycoprotein ligand (PSGL). Although treatment of neutrophils with elastase or Osialoglycoprotease decreased surface CD43 and PSGL, they did not reduce binding of IAV to neutrophils, implying that IAV can bind to alternate binding sites in the absence of CD43. Pretreatment of neutrophils with elastase also did not prevent IAV from increasing expression of integrins and enhancing adhesion. Up-regulation of adhesion molecules and adhesion are important, previously unrecognized, features of neutrophil activation by IAV. Further studies will be needed to clarify the mechanism of these effects.

Animals↗
PubMed1997

Nitric oxide inhibition decreases neutrophil adhesion at the inflammatory site, while increasing adhesion in remote organs in peritonitis.

Nitric oxide (NO) is a regulator of leukocyte adhesion in the microcirculation. This study was designed to examine the effects of a NO synthase inhibitor on neutrophil adhesion in the peritoneum, lung, liver, and kidney in a rat peritonitis model using a fluorescence microscopic method. Sprague-Dawley rats were given normal saline (control) or N omega-nitro-L-arginine methyl ester (L-NAME) at dosages of 10 mg/kg (N10) or 100 mg/kg (N100) (n = 66) intraperitoneally. One hour after pretreatment fluorescein-labeled neutrophils were infused without bacterial challenge (0 hr). Other rats received an injection of 10(7) Escherichia coli into the peritoneal cavity 1 hr after pretreatment. Labeled neutrophils were infused 1 and 5 hr after bacterial challenge. Just 2 min after neutrophil injection, blood samples were obtained and the animals were killed. Five peritoneal samples (omentum, mesentery, parietal peritoneum, colon, and ileum), both lungs, the liver, and the right kidney were harvested for counting of labeled neutrophils under epifluorescent microscopy. Combined plasma nitrite/nitrate levels were determined. In another set of rats (n = 36), an arterial catheter was inserted after L-NAME treatment and bacterial challenge. At 0, 1, 5, and 12 hr after challenge, blood pressure, heart rate, and arterial blood gas data were measured. One hour after E. coli challenge, the number of neutrophils in the peritoneum was significantly lower in both L-NAME-treated groups than in the control group. In contrast, the number of labeled neutrophils in the lungs was significantly higher in the N100 group than in the control group. Neutrophil accumulation in the lungs and peritoneum at 0 and 5 hr and in the liver and kidney at 0, 1, and 5 hr did not differ among groups, nor did combined plasma nitrite/nitrate levels. L-NAME treatment had no influence on either hemodynamic or blood gas data. In conclusion, administration of L-NAME increases neutrophil adhesion in the lung, while decreasing that in the peritoneum. NO plays an important role in neutrophil adhesion at the inflammatory site, as well as in remote organs, during peritonitis. NO inhibition may be detrimental, due to neutrophil sequestration, in this peritonitis model.

Animals↗