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At least 865 records · Page 48Linked to original sources
PubMed1996

Mechanisms regulating eosinophil extravasation in asthma.

Infiltration of eosinophils into tissue allergic inflammation is mediated by a combination of processes. Eosinophil L-selection and very late activation antigen (VLA-4) can selectively regulate eosinophil adhesion to the endothelium. Activating cytokines, such as interleukin (IL)-5, regulated upon activation in normal T-cells (RANTES) and monocyte chemotactic peptide (MCP)-3 specifically act on eosinophils. Moreover, eosinophils from allergic individuals can be primed for increased adhesion and movement by chemokines released at sites of allergic inflammation. Together, these processes induce a specific infiltration of eosinophils.

Animals↗
PubMed1996

Effect of interleukin-5 exposure during in vitro eosinophilopiesis on MAC-1 adhesion molecule expression and function on cultured human eosinophils.

We examined the selective effects of interleukin (IL-5) in regulating the maturational expression of surface adhesion molecules on human eosinophils and adhesion to endothelial cells during eosinophiiopolesis in vitro. Expression of the beta 2 integrins (CD11/CD18) and the beta 1 integrin, VLA-4 (CD49d/ CD29), was assessed during development in culture with IL-3, IL-5, and granulocyte-macrophage colony stimulating factor in cultures of human umbilical cord blood-derived eosinophil (CDE) precursor cells. Expression of both CD11b and CD18 subunits of Mac-1 was lower on CDE which were continuously (= chronically) exposed to IL-5 than on CDE which were cultured without IL-5 for the final week of culture. CD11b expression on cells grown without IL-5 was 71.3 +/- 5.92 (mean specific fluorescence value [MSF] as measured by flow cytometry) versus 52.5 +/- 4.48 MSF for Mac-1 alpha (CD11b) on CDE grown in the continued presence of 2 x 10 - 11 mol/L IL-5 (P < .01). Although expression of VLA-4 decreased as CDE matured, expression of CD29 and CD49d were similar regardless of cytokine exposure for the final week of culture. For eosinophils cultured without IL-5, acute stimulation with 10 - 8 mol/L IL-5 increased CD11b surface expression and increased the number of cells adhering to unstimulated human umbilical vein endothelial cells (HUVEC) from 4,570 +/- 780 cells (9.14 +/- 1.56% adhesion) to 8,385 +/- 515 cells (16.8 +/- 1.03% adhesion) (P < .01). Basal adhesion to unstimulated HUVEC of CDE cultured continuously with IL-5 was comparable (8.62 +/- 1.12% adhesion; P = NS), but neither CD11b expression (50.3 +/- 11.8 MSF; P = NS v control) nor adhesion to HUVEC (6.77 +/- 1.35%; P = NS) was enhanced in these eosinophils after acute stimulation with IL-5. Blockade of adhesion to IL-1-stimulated HUVEC caused by the anti-CD49d monoclonal antibody (MoAb), HP2/1, was comparable for cells cultured with IL-5 and without IL-5. However, the anti-CD18 MoAb, R15.7, caused 47.6 +/- 5.08% inhibition of adhesion of eosinophils cultured without IL-5 and only 25.8 +/- 5.20% for cells cultured continuously with IL-5 (P < .01), and failed to block significantly the adhesion of only the latter cells to IL-4-stimulated HUVEC. Our data show that continuous, chronic exposure to low concentrations of IL-5 causes decreased expression of Mac-1 and refractoriness to acute stimulation with IL-5 of adhesion to HUVEC. These data further demonstrate that CDE maturing in the continued presence of IL-5 adhere to HUVEC predominantly through VLA-4 ligation.

Cell Adhesion↗
PubMed1996

Endothelial interactions of hairy cells: the importance of alpha 4 beta 1 in the unusual tissue distribution of the disorder.

The tissue-homing of all lymphocytes involves their interactions with endothelial cells (ECs) and with various tissue accessory cells. However, in hairy cell leukemia (HCL), these processes are particularly prominent and result in diagnostic appearances in the spleen, liver, and bone marrow. The present study explores the mechanisms that underlie these tissue reactions. Using a human umbilical vein EC (HUVEC) model, various possible receptor-ligand interactions between hairy cells (HCs) and ECs were examined and a central importance for alpha 4 beta 1/vascular cell adhesion molecule-1 (VCAM-1) was established. This receptor-ligand pair was shown to be important both for strong adhesion and for HC motility/transmigration. A similar importance for alpha 4 beta 1/VCAM-1 was established for the interaction between HCs and relevant tissue accessory cells. The in vitro relevance of these findings was confirmed by the demonstration of VCAM-1 in HCL spleen and by the fact that, in frozen sections, HCs adhered (via VCAM-1) to the red pulp, but not to other areas of normal spleen. These results indicate that alpha 4 beta 1/VCAM-1 is central to the interaction between HCs and endothelium/accessory cells. Such interactions, together with the intrinsic cell activation characteristic of HCL and the HC's consequent ability to interact with matrix, are responsible for many of the characteristic features of the disease.

Cell Movement↗
PubMed1996

Phorbol ester stimulation increases sickle erythrocyte adherence to endothelium: a novel pathway involving alpha 4 beta 1 integrin receptors on sickle reticulocytes and fibronectin.

Sickle-cell adherence to endothelium has been hypothesized to initiate or contribute to microvascular occlusion and pain episodes. Adherence involves plasma proteins, endothelial-cell adhesion molecules, and receptors on sickle erythrocytes. It has previously been reported that sickle reticulocytes express the alpha 4 beta 1 integrin receptor and bind to cytokine-activated endothelium via an alpha 4 beta 1/vascular-cell adhesion molecule-1 (VCAM-1) interaction. To elucidate other roles for alpha 4 beta 1 in sickle-cell adherence, the ability of activated alpha 4 beta 1 to promote adhesion to endothelium via a ligand different than VCAM-1 was explored. Adherence assays were performed under dynamic conditions at a shear stress of 1 dyne/cm2. Preincubation of sickle erythrocytes with phorbol 12,13-dibutyrate (PDBu) increased adherence of sickle cells eightfold as compared with untreated sickle cells. Normal erythrocytes, whether treated with PDBu or not, did not adhere to the endothelium. Activating anti-beta 1 antibodies 4B4 and 8A2 also increased the adhesion of sickle, but not normal, red blood cell (RBC) adhesion to endothelium. Anti-alpha 4 antibodies HP1/2 and HP2/1, inhibitory antibody 4B5, or an RGD peptide inhibited sickle-cell adherence induced by PDBu. Additional studies were undertaken to examine if fibronectin, a ligand for activated alpha 4 beta 1, was involved in PDBu-induced sickle erythrocyte adherence. Adherence of PDBu-treated sickle cells was completely inhibited by the CS-1 peptide of fibronectin. Fibronectin was detected on the surface of washed endothelium using an antifibronectin antibody in enzyme-linked immunosorbent assays. Antifibronectin antibody pretreatment of endothelial cells inhibited PDBu-induced adherence by 79% +/- 17%. Incubation of sickle RBCs with exogenous fibronectin after PDBu treatment inhibited adherence 86% +/- 8%. Taken together, these data suggest that endothelial-bound fibronectin mediates adherence of PDBu-treated sickle cells. Interleukin-8 (IL-8), a chemokine released in response to bacterial infection, viral infection, or other injurious agents, and known to activate integrins, also increased adherence of sickle erythrocytes to endothelial cells via fibronectin. This novel adherence pathway involving sickle-cell alpha 4 beta 1 activated by PDBu or IL-8 may therefore be relevant in vivo at vascular sites that produce IL-8 or similar agonists in response to vascular injury or immune activation. These observations describe ways in which inflammation and immune responses cause vasoocclusive complications in sickle-cell disease.

Amino Acid Sequence↗
PubMed1996

[The expression of adhesion molecules on eosinophils from atopic and non-atopic subjects].

The accumulation of eosinophils in the airway is one of the characteristics seen in patients with chronic asthma. There is now considerable evidence that airway eosinophilia is associated with the development of late asthmatic response (LAR) and bronchial hyperresponsiveness. In this study, we observed PAF induced up-regulation of inducible adhesion molecules Mac-1 and LFA-1 beta on eosinophils of atopic patients compared with non-atopic and normal subjects. In conclusion, we found that adhesion molecule expression is different between atopic and non-atopic patients. Therefore, adhesion molecule expression is thought to be important in the prolonging and pathogenesis of allergic inflammation.

Adult↗
PubMed1996

Protective effects of monoclonal antibody to VLA-4 on leukocyte adhesion and course of disease in adjuvant arthritis in rats.

OBJECTIVE: Leukocyte adhesion to the endothelium of postcapillary venules is considered an important step in the inflammatory response. Cell adhesion molecules have been found to play a role in virtually every cellular interaction from inflammation to reperfusion injury. The purpose of this study was to determine the extent of leukocyte adhesion during the development of adjuvant arthritis in rats, and the putative inhibitory effect of a monoclonal antibody (Mab) to very late activation antigen-4 (VLA-4) on leukocyte adhesion and on arthritic disease. METHODS: Adjuvant arthritis was induced in rats by subdermal injection of Freund's adjuvant and arthritis index quantified on the 18th day of disease. Number of rolling, adherent leukocytes/100 microns venule and blood cell velocity were quantified in mesenteric venules (20-30 microns diameter and 100 microns length) of Wistar-Lewis rats, using intravital microscopy. RESULTS: We administered a Mab to rat VLA-4, alpha 4-subunit, at a dose of 1 mg/kg intravenously on Days 1, 9, and 17 to the arthritic rats. Both variables measured in mesenteric venules were reduced. Leukocyte rolling was partially inhibited (by 57%), whereas leukocyte adhesion was totally inhibited (by 94%). In addition, the arthritis index decreased by 54%. Nonbinding isotype mouse IgG1 control antibody did not affect either of the variables. CONCLUSION: Leukocyte adhesion in mesenteric venules of adjuvant arthritic rats involves VLA-4 interaction with an unknown endothelial ligand, which is completely inhibited by Mab to rat VLA-4, indicating a promising effect on clinical symptoms.

Animals↗
PubMed1997

Triggering of motile behavior in T lymphocytes via cross-linking of alpha 4 beta 1 and alpha L beta 2.

The mechanisms by which T lymphocytes are transformed from passively transported cells during circulation in the vascular system to actively migrating cells during extravasation are unknown. Therefore, the possibility that lymphocyte receptors are capable of inducing motility was investigated using a modified Boyden chamber assay. Cross-linking of alphaL beta2 and alpha4 beta1 on human T lymphocytes (T cell line and peripheral blood T cells) with immobilized mAbs induced motile behavior on fibronectin, laminin, collagen type IV, and poly-L-lysine. This induction of T cell migration was very potent and in most cases more efficient than pretreatment of the cells with phorbol esters. In contrast, control Abs to several other integrin- and non-integrin molecules present on T lymphocytes did not induce T cell migration. Anti-CD3 Abs themselves did not trigger motile behavior. However, anti-CD3 promoted T cell migration in the Boyden chamber system if present simultaneously with 40-kDa alpha4 beta1 binding fibronectin fragments or alphaL beta2 binding intercellular adhesion molecule-1/hIgG1Fc fusion proteins on the upper side of the filter. Abs to other surface components on T cells did not trigger motility when presented together with the 40-kDa fibronectin fragments or the intercellular adhesion molecule-1/hIgG1Fc fusion proteins. The induction of motile behavior could be blocked if the T cells were pretreated with Genistein and Calphostin C, indicating the involvement of a protein tyrosine kinase and protein kinase C-dependent signaling pathway in triggering of T cell motility via integrins. These results indicate that alphaL beta2 and alpha4 beta1 on T lymphocytes can selectively trigger motile behavior when cross-linked by their endothelial or extracellular matrix ligands. Furthermore, these data indicate that cross-linking of CD3 facilitates ligand binding and subsequent triggering of a motile phenotype by alphaL beta2 and alpha4 beta1.

Adult↗
PubMed1997

Granulocyte-macrophage colony-stimulating factor regulates the functional adhesive state of very late antigen-4 expressed by eosinophils.

As very late antigen-4 (VLA-4) can exist in different functional states, we have sought to determine whether a cytokine expressed by inflamed endothelium (i.e., granulocyte-macrophage CSF (GM-CSF)) could regulate the functional state of VLA-4 expressed by eosinophils. Using a micropipette single cell adhesion assay able to measure the strength of adhesion forces, eosinophils exhibited low levels of basal adhesion to unstimulated endothelium (separation force, 0.022 +/- 0.003 mdynes). In contrast, individual eosinophils bound to IL-1beta-stimulated endothelium (0.49 +/- 0.02 mdynes), TNF-stimulated endothelium (0.62 +/- 0.05 mdynes), or IL-4-stimulated endothelium (0.11 +/- 0.01 mdynes) with increased avidity as assessed by separation force. Eosinophil binding to IL-4-stimulated endothelium was significantly inhibited by neutralizing Abs to either vascular cell adhesion molecule (VCAM) or VLA-4. The strength of eosinophil adhesion to VCAM (0.31 +/- 0.02 mdynes) or to connecting segment-1 (CS-1) (0.18 mdynes) was greater than the strength of eosinophil adhesion to unstimulated endothelium (0.02 mdynes), but was less than the strength of eosinophil adhesion to IL-1beta-stimulated endothelium (0.49 +/- 0.02 mdynes). After incubating eosinophils for 30 min with GM-CSF, the mean adhesion strength of eosinophils to CS-1 and VCAM increased significantly by 84 and 54%, respectively, compared with that of controls. This increased binding of eosinophils to VCAM or CS-1 was not due to alterations in VLA-4 receptor number (assessed by FACS analysis) or alterations in VLA-4 receptor distribution (assessed by confocal microscopy). These studies suggest that endothelial-derived cytokines such as GM-CSF have the potential to alter the functional state of eosinophil-expressed VLA-4 from a low affinity state to a high affinity state.

Carrier Proteins↗
PubMed1996

Immunopathogenesis of vernal keratoconjunctivitis.

We have analyzed the in situ distribution of immune cells in the conjunctival biopsy specimens obtained from patients with active vernal keratoconjunctivitis (VKC). We used immunohistochemical techniques and a panel of monoclonal and polyclonal antibodies. Our data point to a complex immunopathogenesis of the disease. Distinct components involved in IgE-mediated immune mechanisms, as well as humoral and cell mediated immune mechanisms were detected in the conjunctival tissues. In addition, we investigated the presence and distribution of adhesion molecules. In the normal conjunctiva, intercellular adhesion molecule-1 (ICAM-1) was expressed only on the vascular endothelium, lymphocyte function associated antigen-1 (LFA-1) and intercellular adhesion molecule-3 (ICAM-3) on epithelial and stromal mononuclear cells, and very late activation antigen-4 (VLA-4) on a few stromal mononuclear cells. Endothelial leukocyte adhesion molecule-1 (ELAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression was not detected. In VKC a marked increase of all these antigens was observed. Strong ICAM-1 expression was induced on the basal epithelial cells, and vascular endothelium. Furthermore, about 30% of the stromal mononuclear cells expressed ICAM-1. LFA-1 and ICAM-3 were expressed on the majority of infiltrating mononuclear cells. VLA-4 expression was noted on about 25% of the stromal mononuclear cells. ELAM-1 and VCAM-1 were induced on the vascular endothelial cells. Our results suggests that increased expression of adhesion molecules in VKC promotes the recruitment of inflammatory cells through blood vessels and the cell interaction between lymphocytes and antigen presenting cells, among lymphocytes, as well as between lymphocytes and epithelial cells.

Antigens, CD↗
PubMed1997

T cell adhesion to endothelial cells and extracellular matrix is modulated upon transendothelial cell migration.

During inflammation, T cells transmigrate from the bloodstream into perivascular tissues. As T cells transmigrate, they undergo a series of attachments to and detachments from the endothelium and then extravasate into the extracellular matrix (ECM). T cell migration into the ECM involves a number of mechanisms that influence cell-ECM interactions. The modulation of integrin expression and affinity are two such mechanisms in which cells can alter their ability to interact with other cells and ECM. We show in vitro that transmigrated T cells exhibit down-regulation of very late activation antigen-4 and leukocyte function-associated antigen-1 integrin surface expression and a decrease in binding to recombinant vascular cell adhesion molecule-1 and recombinant intercellular adhesion molecule-1. Also, transmigrated T cells displayed an increase in binding to collagens I and IV and fibronectin. Further, brain sections of experimental autoimmune encephalomyelitis mice demonstrated that as T cells migrated farther into the tissue, very late activation antigen-4 expression was lost while CD4 expression remained unchanged. The significance of these findings in the modulation of the inflammatory response is discussed.

Animals↗
PubMed1996

Leucocyte/endothelial cell adhesion receptors in muscle biopsies from patients with idiopathic inflammatory myopathies (IIM).

Interactions between leucocytes and endothelial cells through specific adhesion receptors play an increasingly recognized crucial role in the development of inflammatory infiltrates in chronic inflammatory diseases. In this study we investigated adhesion molecule expression in muscle biopsies from 18 dermatomyositis, six polymyositis, five inclusion-body myositis patients and from eight normal controls. Immunohistochemical detection of leucocyte integrins LFA-1 and VLA-4, their endothelial counter-receptors intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), and the endothelial cell markers CD31 and von Willebrand factor-related antigen (vWFAg) was performed using specific MoAbs and an alkaline phosphatase anti-alkaline phosphatase technique. ICAM-1 expression was up-regulated and VCAM-1 induced in muscle capillaries of dermatomyositis samples. In both dermatomyositis and polymyositis, endothelial cells from vessels surrounded by inflammatory infiltrates strongly expressed ICAM-1 and VCAM-1. Infiltrating leucocytes were intensively LFA-1- and VLA-4-positive. These data suggest that leucocyte/endothelial cell interactions mediated by the receptor/ligand pairs LFA-1/ICAM-1 and VLA-4/VCAM-1 actively participate in the development of muscle inflammatory infiltrates in the major inflammatory myopathies. In addition, ICAM-1 and VCAM-1 over-expression by capillary endothelial cells in dermatomyositis supports the hypothesis that capillary activation and/or injury is a major feature in this disease.

Adolescent↗
PubMed1997

Decrease of very late activation antigen-4 and CD36 on reticulocytes in sickle cell patients treated with hydroxyurea.

Sickle cell disease (SCD) is characterized by repeated vaso-occlusive events, which result in substantial morbidity. Abnormal adhesion of sickle red blood cells (RBC) to the vascular endothelium is postulated to play a role in the pathogenesis of vaso-occlusion. Two adhesion receptors, very late activation antigen-4 (VLA-4) and CD36, are found in unusually high numbers on sickle cell reticulocytes and do mediate adhesion of sickle RBC to endothelium. Hydroxyurea (HU) therapy results in fewer vaso-occlusive episodes, and we postulated that HU-related modulation of VLA-4 and CD36 receptors may contribute to its clinical benefit. Using flow cytometry, eight patients were followed from the onset of HU treatment through a mean treatment length of 200 +/- 49 days. Mean corpuscular volume and percent fetal hemoglobin (Hb F) increased from 87% +/- 6% to 98% +/- 9% and 6.6% +/- 3.9% to 12.7% +/- 5.6%, respectively. The percentage of reticulocytes expressing VLA-4 decreased from 29.0% +/- 5.9% to 14.9% +/- 2.3% (P = .0003). Two thirds of the total decrease in VLA-4 expression occurred after 10 weeks of HU and plateaued by 20 weeks. Changes in VLA-4 expression occurred before substantial increases in Hb F. The percentage of reticulocytes expressing CD36 decreased from 55.3% +/- 6.4% to 42.6% (P = .0046). Changes in adhesion receptor expression were not caused by a decrease in reticulocytosis with HU therapy. This report is the first to associate a decrease in adhesion receptor expression with a therapy known to reduce the clinical severity of SCD.

Adolescent↗
PubMed1997

Adult Schistosoma mansoni worms positively modulate soluble egg antigen-induced inflammatory hepatic granuloma formation in vivo. Stereological analysis and immunophenotyping of extracellular matrix proteins, adhesion molecules, and chemokines.

Synchronized liver granulomas were induced by injecting Sepharose beads to which SEA soluble egg antigen (SEA) or the concanavalin A binding fraction of SEA had been coupled into a mesenteric vein in naive, single-sex (35 days) and bisexually (28 days) Schistosoma mansoni-infected and Plasmodium berghei-immunized mice. Stereological analysis revealed that peak granuloma formation was already reached 8 days after injection in single-sex infected mice compared with 16 days in naive animals. No difference in granuloma formation between naive and P. berghei-immunized animals and between unisexually and bisexually S. mansoni-infected mice was observed. This suggests that the positive immunomodulatory effect on the granulomogenesis is worm specific and not likely to be due to arousal of the immune system by unrelated factors, nor is it influenced by the gender or degree of maturation of female worms. At all stages in time, the concanavalin A binding-fraction-induced granulomas reached only 65 to 70% of the volume of SEA-induced granulomas. Immunophenotyping of extracellular matrix proteins around deposited heads revealed that fibronectin was the dominant extracellular matrix protein and that also type I and IV collagen and laminin were deposited. Temporal analysis of the expression of the adhesion molecules ICAM-1, LFA-1, VLA-4, and VLA-6 was performed. Morphological evidence is presented for the role of adhesion molecules in the initiation and maintenance of hepatic granuloma formation. The chemokine monocyte chemoattractant protein-1 was expressed in the granuloma and in hepatic artery branches. From these data, it is concluded that adult S. mansoni worms positively modulate schistosomal hepatic granuloma formation in vivo. Adhesion molecules and chemokines play important roles in schistosomal granuloma formation.

Animals↗
PubMed1997

Enhanced induction of very late antigen 4/lymphocyte function-associated antigen 1-dependent T-cell migration to tumor sites following administration of interleukin 12.

Administration of interleukin 12 (IL-12) into mice bearing CSA1M, OV-HM, Meth A, or MCH-1-A1 tumor induced complete regression of CSA1M and OV-HM tumors but induced only a slight growth inhibition of Meth A and MCH-1-A1 tumors. These effects of IL-12 were associated with high and only marginal levels of T-cell infiltration into CSA1M/OV-HM and Meth A/MCH-1-A1 tumor masses, respectively. Here, we investigated the role of IL-12 in the induction of T-cell migration. Spleen cells from untreated or IL-12-treated CSA1M-bearing mice were stained in vitro with a fluorescein chemical and transferred i.v. into IL-12-untreated CSA1M-bearing mice. Migration of donor cells was quantitated by counting the number of fluorescent cells on cryostat sections of tumor masses. Although only a slight migration was detected for spleen cells from IL-12-untreated CSA1M-bearing as well as IL-12-treated or untreated normal mice, enhanced migration was observed for cells from IL-12-treated CSA1M-bearing mice. A similar enhanced migration was observed for the OV-HM model. In contrast, such an enhancement was only marginal in the Meth A and MCH-1-A1 models. Immunohistochemical studies of tumors from IL-12-treated mice revealed that the predominant T-cell subset was CD4+ in CSA1M and CD8+ in OV-HM tumor masses. Consistent with this observation, the dominant subset of migrating T cells was found to be CD4+ in the CSA1M and CD8+ in the OV-HM models. T-cell migration was inhibited by pretreatment of recipients with either combination of anti-very late antigen 4 + anti-vascular cell adhesion molecule 1 or anti-lymphocyte function-associated antigen 1 + anti-intercellular adhesion molecule 1 monoclonal antibody. These results indicate that IL-12 can confer T cells with a capacity to migrate to tumor sites through very late antigen 4/lymphocyte function-associated antigen 1 adhesion pathways and that the in vivo acquisition of such a capacity following IL-12 treatment correlates with the induction of tumor regression.

Animals↗
PubMed1997

Thrombopoietin promotes adhesion of primitive human hemopoietic cells to fibronectin and vascular cell adhesion molecule-1: role of activation of very late antigen (VLA)-4 and VLA-5.

Thrombopoietin (Tpo), the ligand for c-mpl and a principal regulator of megakaryocytopoiesis and platelet production, has been demonstrated to stimulate the growth and differentiation of megakaryocyte as well as multipotent hemopoietic progenitor cells. In the present study we demonstrate that Tpo can stimulate the adhesion of the Mo7e progenitor cell line to fibronectin (Fn) as well as vascular cell adhesion molecule-1 through activation of very late antigen (VLA)-4 and VLA-5, adhesion molecules previously demonstrated to be involved in regulation of steady state hemopoiesis. Tpo-induced adhesion was concentration dependent, reached a maximum following 30 min, and appeared to be dependent on adenylate cyclase, and tyrosine kinase activity. Furthermore, second messenger inhibitors implicated essential and complimentary roles of phosphatidylinositol-3-kinase and protein kinase C in mediating Tpo-induced adhesion. The ability of Tpo to promote adhesion to fibronectin was comparable to that of IL-3, but less than that of stem cell factor. Unlike the ability of these cytokines to synergistically enhance growth of Mo7e as well as normal progenitor cells, no synergy was observed with regard to their ability to enhance adhesion. Finally, Tpo stimulated adhesion of primitive (CD34+ CD38-) human bone marrow cells to fibronectin, predominantly through activation of VLA-5, whereas no such effect could be observed on CD34+ CD38+ bone marrow cells. Thus, Tpo might play an important role in early hemopoiesis, at least in part through its ability to promote adhesion through activation of adhesion molecules on hemopoietic progenitor cells.

ADP-ribosyl Cyclase↗