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PubMed2003

Lymphocyte homing to bronchus-associated lymphoid tissue (BALT) is mediated by L-selectin/PNAd, alpha4beta1 integrin/VCAM-1, and LFA-1 adhesion pathways.

Bronchus-associated lymphoid tissue (BALT) participates in airway immune responses. However, little is known about the lymphocyte-endothelial adhesion cascades that recruit lymphocytes from blood into BALT. We show that high endothelial venules (HEVs) in BALT express substantial levels of VCAM-1, in marked contrast to HEVs in other secondary lymphoid tissues. BALT HEVs also express the L-selectin ligand PNAd. Anti-L-selectin, anti-PNAd, and anti-LFA-1 mAbs almost completely block the homing of B and T lymphocytes into BALT, whereas anti-alpha4 integrin and anti-VCAM-1 mAbs inhibit homing by nearly 40%. alpha4beta7 integrin and MAdCAM-1 are not involved. Importantly, we found that mAbs against alpha4 integrin and VCAM-1 significantly block the migration of total T cells (80% memory phenotype) but not naive T and B cells to BALT. These results suggest that an adhesion cascade, which includes L-selectin/PNAd, alpha4beta1 integrin/VCAM-1, and LFA-1, targets specific lymphocyte subsets to BALT. This high level of involvement of alpha4beta1 integrin/VCAM-1 is unique among secondary lymphoid tissues, and may help unify lymphocyte migration pathways and immune responses in BALT and other bronchopulmonary tissues.

Animals↗
PubMed1998

Adhesion molecule phenotype of T lymphocytes in inflamed CNS.

The phenotype of T cells in the central nervous system (CNS) in two models of chronic inflammation (experimental allergic encephalomyelitis and Corynebacterium parvum-induced inflammation) was compared to that of T cells in gut and chronically inflamed subcutaneous tissue and lung. CNS T cells display a similar phenotype in both inflammatory models, and are phenotypically unique compared to T cells from the other inflamed tissues. T cells from inflamed CNS are mainly CD4+ and are the only population examined that express a typical activated/memory phenotype: CD44high/LFA-1high/ICAM-1high/CD45RBlow. The CNS T cells are alpha4beta7-integrin(negative), but express alpha4-integrin and activated beta1 integrin, suggesting expression of the alpha4beta1-heterodimer in an activated state. In contrast, most T cells in gut express low levels of activated beta1 integrin. The CNS T cells lack expression of alpha6 and alphaE integrin chains and L-selectin. In inflamed CNS and inflamed subcutaneous tissue, approximately 50% of T cells express high affinity ligands for P-selectin while fewer than 10% express high affinity ligands for E-selectin. In summary, our data show that, independent of the inflammatory stimulus, T cells recruited into the inflamed CNS are phenotypically distinct from T cells in other inflamed tissues. This finding leads us to hypothesize the existence of a phenotypically distinct 'CNS-seeking' T lymphocyte population.

Animals↗
PubMed2005

Therapeutic anti-integrin (alpha4 and alphaL) monoclonal antibodies: two-edged swords?

Anti-alpha4 and anti-alphaL integrin chain monoclonal antibodies have shown a clear-cut beneficial effect in different animal models of autoimmune and inflammatory disorders as well as in human diseases, including multiple sclerosis, inflammatory bowel disease, and psoriasis. It has been widely assumed that this therapeutic effect is mainly consequence of the blockade of leucocyte adhesion to endothelium, inhibiting thus their extravasation and the inflammatory phenomenon. However, it is evident that both alpha4beta1 (very late antigen-4) and alphaLbeta2 (leucocyte function-associated antigen-1) integrins have additional important roles in other immune phenomena, including the formation of the immune synapse and the differentiation of T helper 1 lymphocytes. Therefore, it is very feasible that the long-term administration of blocking agents directed against these integrins to patients with inflammatory/autoimmune conditions may have undesirable or unexpected effects.

Antibodies, Monoclonal↗
PubMed2005

A small molecule alpha 4 beta 1 antagonist prevents development of murine Lyme arthritis without affecting protective immunity.

After infection with Borrelia burgdorferi, humans and mice under certain conditions develop arthritis. Initiation of inflammation is dependent on the migration of innate immune cells to the site of infection, controlled by interactions of a variety of adhesion molecules. In this study, we used the newly synthesized compound S18407, which is a prodrug of the active drug S16197, to analyze the functional importance of alpha4beta1-dependent cell adhesion for the development of arthritis and for the antibacterial immune response. S16197 is shown to interfere specifically with the binding of alpha4beta(1 integrin to its ligands VCAM-1 and fibronectin in vitro. Treatment of B. burgdorferi-infected C3H/HeJ mice with the alpha4beta1 antagonist significantly ameliorated the outcome of clinical arthritis and the influx of neutrophilic granulocytes into ankle joints. Furthermore, local mRNA up-regulation of the proinflammatory mediators IL-1, IL-6, and cyclooxygenase-2 was largely abolished. Neither the synthesis of spirochete-specific Igs nor the development of a Th1-dominated immune response was altered by the treatment. Importantly, the drug also did not interfere with Ab-mediated control of spirochete load in the tissues. These findings demonstrate that the pathogenesis, but not the protective immune response, in Lyme arthritis is dependent on the alpha4beta1-mediated influx of inflammatory cells. The onset of inflammation can be successfully targeted by treatment with S18407.

Amino Acids↗
PubMed1999

Cell adhesion mediated drug resistance (CAM-DR): role of integrins and resistance to apoptosis in human myeloma cell lines.

Integrin-mediated adhesion influences cell survival and may prevent programmed cell death. Little is known about how drug-sensitive tumor cell lines survive initial exposures to cytotoxic drugs and eventually select for drug-resistant populations. Factors that allow for cell survival following acute cytotoxic drug exposure may differ from drug resistance mechanisms selected for by chronic drug exposure. We show here that drug-sensitive 8226 human myeloma cells, demonstrated to express both VLA-4 (alpha4beta1) and VLA-5 (alpha5beta1) integrin fibronectin (FN) receptors, are relatively resistant to the apoptotic effects of doxorubicin and melphalan when pre-adhered to FN and compared with cells grown in suspension. This cell adhesion mediated drug resistance, or CAM-DR, was not due to reduced drug accumulation or upregulation of anti-apoptotic Bcl-2 family members. As determined by flow cytometry, myeloma cell lines selected for drug resistance, with either doxorubicin or melphalan, overexpress VLA-4. Functional assays revealed a significant increase in alpha4-mediated cell adhesion in both drug-resistant variants compared with the drug-sensitive parent line. When removed from selection pressure, drug-resistant cell lines reverted to a drug sensitive and alpha4-low phenotype. Whether VLA-4-mediated FN adhesion offers a survival advantage over VLA-5-mediated adhesion remains to be determined. In conclusion, we have demonstrated that FN-mediated adhesion confers a survival advantage for myeloma cells acutely exposed to cytotoxic drugs by inhibiting drug-induced apoptosis. This finding may explain how some cells survive initial drug exposure and eventually express classical mechanisms of drug resistance such as MDR1 overexpression.

Antineoplastic Agents↗
PubMed2000

Inhibitory effects of MLDG-containing heterodimeric disintegrins reveal distinct structural requirements for interaction of the integrin alpha 9beta 1 with VCAM-1, tenascin-C, and osteopontin.

The integrin alpha9beta1 is expressed on epithelial cells, smooth muscle cells, skeletal muscle, and neutrophils and recognizes at least three distinct ligands: vascular cell adhesion molecule 1 (VCAM-1), tenascin-C, and osteopontin. The alpha9 subunit is structurally similar to the integrin alpha4 subunit, and alpha9beta1 and alpha4beta1 both recognize VCAM-1 as a ligand. We therefore examined whether the disintegrin EC3, which we have recently shown specifically inhibits the binding of alpha4 integrins to ligands, would also be a functional inhibitor of alpha9beta1. EC3 and a novel heterodimeric disintegrin that we identified, EC6, both were potent inhibitors of alpha9beta1-mediated adhesion to VCAM-1 and of neutrophil migration across tumor necrosis factor-activated endothelial cells. A peptide containing a novel MLDG motif shared by both of these disintegrins also inhibited alpha9beta1- and alpha4beta1-mediated adhesion to VCAM-1. Surprisingly though, concentrations of EC3 that completely inhibited adhesion of alpha9-transfected cells to VCAM-1 had little or no effect on adhesion to either of the other alpha9beta1 ligands, osteopontin and tenascin-C. Furthermore, peptides AEIDGIEL and SVVYGLR, which we have previously shown inhibit binding of alpha9beta1-expressing cells to tenascin-C and osteopontin, respectively, had no effect on adhesion to VCAM-1. These data suggest that there are structurally distinct requirements for interactions of the alpha9beta1 integrin with VCAM-1 and the extracellular matrix ligands osteopontin and tenascin-C.

Amino Acid Motifs↗
PubMed1999

Integrin-mediated adhesion of uterine endometrial cells from endometriosis patients to extracellular matrix proteins is enhanced by tumor necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1).

OBJECTIVES: (1) to demonstrate specificity of integrin function in endometrial cell adhesion; (2) to investigate their regulation by tumor necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1); and (3) to detect differences between cells from patients with and without endometriosis. STUDY DESIGN: Endometrial cell cultures from ten patients with and 13 without endometriosis were tested for their expression of integrins alpha2beta1, alpha5beta1, alpha(v)beta3, and alpha4beta1 by immunocytochemistry and for their adhesion to collagen type IV, laminin, and fibronectin. RESULTS: Integrin expression was independent of cytokine treatment. Addition of antiintegrin antibodies inhibited adhesion. A significant increase in adhesion to laminin and fibronectin was seen in endometriosis after IL-1 treatment and additionally to collagen after TNF alpha. Cells from women without endometriosis showed a significant increase only to fibronectin. CONCLUSIONS: Human endometrial cells express functional integrins in vitro. TNF alpha and IL-1 had more pronounced effects on adhesion in endometriosis. Inflammatory cytokines in the peritoneal cavity may facilitate adhesion of retrogradely menstruated endometrial fragments in endometriosis.

Adult↗
PubMed2000

Use of integrins to date the endometrium.

OBJECTIVE: To compare traditional histologic dating criteria of the endometrium with immunohistochemical criteria based on epithelial integrin expression during the menstrual cycle. DESIGN: Prospective clinical study. SETTING: An academic teaching hospital. PATIENT(S): Fertile and infertile women undergoing endometrial biopsy. MAIN OUTCOME MEASURE(S): Immunohistochemical staining intensity and distribution (HSCORE) of three integrins and traditional histologic endometrial dating. RESULT(S): In 1,501 endometrial specimens, phase assignment-based integrin staining was 95% and 85% concordant with histology for the proliferative and early secretory phase, respectively, but only 54% and 49% concordant for the middle and late secretory phase, respectively. The greatest disagreement occurred during the midluteal phase. Of 1,090 patients who underwent sampling 6-10 days after detection of a urinary LH surge (corresponding to cycle days 20-24), multiple logistic regression analysis revealed that endometriosis was positively correlated and male factor infertility was negatively correlated with absent beta3 integrin subunit expression. Diagnosis and absent epithelial alpha4beta1 expression were not related. Patient age was not correlated with the incidence of abnormalities in integrin expression. CONCLUSION(S): Traditional histologic dating of the endometrium has remained the gold standard for nearly 50 years. Although the use of marker proteins provides additional information and may reflect endometrial function or receptivity, such markers cannot yet replace traditional methods of endometrial assessment.

Adolescent↗
PubMed2005

ADAM-Integrin Interactions: potential integrin regulated ectodomain shedding activity.

ADAMs (a disintegrin and metalloprotease) are a family of cell surface proteins related to the Class III snake venom metalloproteases (SVMP). ADAMs are members of the Metazincin family which includes the matrix matalloproteases and the ADAMTS proteins. Unlike their snake venom relatives, ADAMs are expressed as transmembrane cell surface proteins. The domain structure of ADAMs suggests that these proteins posses both proteolytic and adhesive functions. Several members of the ADAM protein family have been shown to be involved in ectodomain shedding of many important cell surface proteins resulting in the release of biologically active soluble factors. The carboxyl-terminal domains, especially the disintegrin-like domain of ADAMs, have been demonstrated to support cell adhesion. The disintegrin-like domains of many ADAMs are capable of acting as integrin ligands. Integrins known to interact with ADAM disintegrin-like domains include alpha4beta1, alpha4beta7, alpha5beta1, alpha6beta1, alpha9beta1, alphavbeta3, and alphavbeta5. This integrin mediated interaction of the disintegrin-like domains with the cell surface suggests that ADAMs may function as cellular counter receptors. In this review we discuss the individual functions ascribed to members of the ADAM family especially those related to integrin interactions and the potential for integrin mediated regulation of ectodomain shedding.

Animals↗
PubMed1997

Direct role of the carboxy-terminal cell-binding domain of fibronectin in neural crest cell motility.

We have analyzed the interaction of neural crest cells with fragments of fibronectin corresponding to the different spliced variants of the COOH-terminal cell-binding domain (COOH-ter CBD). We have shown that this domain can support cell adhesion and migration and that both the IIICS and HepII regions are involved in these events. The rate of locomotion is high, although undirectional, compared to that of whole fibronectin. Interactions with the COOH-ter CBD are controlled by alpha4beta1 and maybe other beta1 integrins and cell-surface proteoglycans. These receptors act cooperatively to mediate attachment, spreading, and migration on fibronectin.

Animals↗
PubMed1996

Correlation between nm23 protein and several cell adhesion molecules in human gastric carcinoma.

The correlation between nm23 protein (nm23) expression and the expression of several cell adhesion molecules was studied immunohistochemically in 110 resected gastric carcinomas. Formalin-fixed and paraffin-embedded samples were serially sectioned and stained with antibodies against nm23, integrin beta1 subfamily members (alpha2beta1, alpha3beta1 and alpha4beta1), LFA-1, ICAM-1, sialyl Lewis(x) (sLex) and CD44H, -V3, and -V6. Primary carcinomas presenting with either lymph node involvement or liver metastasis expressed significantly reduced levels of nm23 compared to tumors without metastasis. The percent of tumors expressing each adhesion molecule was as follows: alpha2beta1, 27.3%; alpha3beta1, 20.0%; alpha4beta1, 14.5%; LFA-1, 14.5%; ICAM-1, 12.7%; sLex, 67.3%; CD44H, 55.5%; CD44V3, 20.0%; and CD44V6, 4.5%. Expression of alpha2beta1 integrin and high levels of sLex were significantly correlated with lymph node metastasis, and expression of alpha3beta1 integrin and high levels of sLex were correlated with liver metastasis. Expression of ICAM-1 was inversely correlated with liver metastasis. Comparing the expression of each cell adhesion molecule with nm23 immunoreactivity, expression of sLex was significantly associated with nm23 expression. Of tumors expressing high levels of sLex, 75% showed reduced nm23 expression, compared to 52% of tumors with weak or no sLex expression (P < 0.05). A similar tendency was also observed in the metastasized secondary tumors. These results suggest that reduced nm23 expression may promote the metastatic properties of cancer cells in concert with increased sLex expression.

Cell Adhesion Molecules↗
PubMed1999

Regulation of integrin-mediated T cell adhesion by the transmembrane protein tyrosine phosphatase CD45.

The transmembrane protein tyrosine phosphatase CD45 is required for Ag receptor signal transduction in lymphocytes. Recently, a role for CD45 in the regulation of macrophage adhesion has been demonstrated as well. To investigate further the role of CD45 in the regulation of adhesion, we examined integrin-mediated adhesion to fibronectin of two T cell lines and their CD45-deficient variants. The absence of CD45 correlated with enhanced adhesion to fibronectin via integrin alpha5beta1 (VLA-5), but not alpha4beta1 (VLA-4) in both cell lines. Adhesion returned to normal levels upon transfection of wild-type CD45 into the CD45-deficient lines. Transfection of chimeric or mutant molecules expressing some, but not all, CD45 domains and activities demonstrated that both the transmembrane domain and the tyrosine phosphatase activity of CD45 were required for regulation of integrin-dependent adhesion, but the highly glycosylated extracellular domain was dispensable. In contrast, only a catalytically active CD45 cytoplasmic domain was required for TCR signaling. Transfectants that restored normal levels of adhesion to fibronectin coimmunoprecipitated with the transmembrane protein known as CD45-associated protein. These studies demonstrate a novel role for CD45 in adhesion regulation and suggest a possible function for its association with CD45-associated protein.

Animals↗
PubMed2002

Anti-integrin as novel drug-discovery targets: potential therapeutic and diagnostic implications.

The role of integrin and extracellular matrix proteins in various pathological processes (including angiogenesis, thrombosis, apoptosis and cell migration and proliferation), leading to both acute and chronic disease states (e.g. ocular diseases, metastasis, unstable angina, myocardial infarction, stroke, osteoporosis, a wide range of inflammatory diseases, vascular remodeling and neurodegenerative disorders) has been recently documented. A key success in this field is evident from the potential role of the platelet GPIIb/IIIa (alphaIIbbeta3) integrin in the prevention, treatment and perhaps diagnosis of various thromboembolic disorders. Additionally, progress has been shown in the development of leukocyte alpha4beta1 antagonists for various inflammatory indications and alphav integrin antagonists for angiogenesis and vascular-related disorders. However, the exact modes of action of certain integrin antagonists are still not fully clear. Integrin antagonists in clinical or pre-clinical development are expected to be used as a stand-alone therapy or, better, as an adjunct to other pharmacotherapy, radiotherapy or interventional procedures.

Animals↗
PubMed2002

Identification of potent and novel alpha4beta1 antagonists using in silico screening.

The antigen alpha4beta1 (very late antigen-4, VLA-4) plays an important role in the migration of white blood cells to sites of inflammation. It has been implicated in the pathology of a variety of diseases including asthma, multiple sclerosis, and rheumatoid arthritis. We describe a series of potent inhibitors of alpha4beta1 that were discovered using computational screening for replacements of the peptide region of an existing tetrapeptide-based alpha4beta1 inhibitor (1; 4-[N'-(2-methylphenyl)ureido]phenylacetyl-Leu-Asp-Val) derived from fibronectin. The search query was constructed using a model of 1 that was based upon the X-ray conformation of the related integrin-binding region of vascular cell adhesion molecule-1 (VCAM-1). The 3D search query consisted of the N-terminal cap and the carboxyl side chain of 1 because, upon the basis of existing structure-activity data on this series, these were known to be critical for high-affinity binding to alpha4beta1. The computational screen identified 12 reagents from a virtual library of 8624 molecules as satisfying the model and our synthetic filters. All of the synthesized compounds tested inhibit alpha4beta1 association with VCAM-1, with the most potent compound having an IC(50) of 1 nM, comparable to the starting compound. Using CATALYST, a 3D QSAR was generated that rationalizes the variation in activities of these alpha4beta1 antagonists. The most potent compound was evaluated in a sheep model of asthma, and a 30 mg nebulized dose was able to inhibit early and late airway responses in allergic sheep following antigen challenge and prevented the development of nonspecific airway hyperresponsiveness to carbachol. Our results demonstrate that it is possible to rapidly identify nonpeptidic replacements of integrin peptide antagonists. This approach should be useful in identification of nonpeptidic alpha4beta1 inhibitors with improved pharmacokinetic properties relative to their peptidic counterparts.

Administration, Inhalation↗
PubMed1997

An RGD to LDV motif conversion within the disintegrin kistrin generates an integrin antagonist that retains potency but exhibits altered receptor specificity. Evidence for a functional equivalence of acidic integrin-binding motifs.

Integrin ligands almost invariably employ a variant of either the RGD or LDV motif as a key element of their receptor recognition site. These short acidic peptide sequences collaborate with specific nonhomologous flanking residues and spatially separate "synergy" sequences to determine receptor binding specificity. Although the consensus sequences for RGD and LDV motifs are quite different, their common use suggests that they might share a critical role in receptor-ligand engagement. To date, the effects of interconversion of the two motifs within a natural protein framework have not been tested; however, in this study, we have converted the natural RGD site found in the snake venom disintegrin kistrin into an LDV motif and examined the effects of the change on the specificity of integrin recognition and on disintegrin potency. While an assessment of receptor binding using cell adhesion and purified integrin solid-phase assays demonstrated recognition of recombinant RGD kistrin by alphaVbeta3 and alpha5beta1, a series of LDV kistrin chimeras did not bind to these integrins, but instead were recognized specifically by alpha4beta1. The minimal change to elicit this distinct switch in receptor specificity was found to involve alteration of only three residues within kistrin. Alanine scanning mutagenesis was used to provide further information on the functional contribution of the three residues. More important, the LDV kistrin chimeras also retained much of the characteristic potency of RGD kistrin, indicating that the kistrin scaffold is optimized for presentation of both RGD and LDV sequences. These findings provide evidence for similarities in motif pharmacophore and reinforce the hypothesis that RGD and LDV sites have an equivalent functional role in receptor binding. They also demonstrate the potential for other disintegrin-containing proteins, perhaps from the ADAM family, to employ LDV sequences for integrin binding.

Amino Acid Sequence↗
PubMedDate not supplied

Spatial expression of the alternatively spliced EIIIB and EIIIA segments of fibronectin in the early chicken embryo.

Using domain-specific antibodies, we have analyzed the tissue distribution of fibronectins (FNs) containing the alternatively spliced EIIIB and EIIIA segments relative to total FN in early chicken embryos. The results show a selective loss of EIIIA+ FN staining in the notochordal sheath and in cartilaginous structures between 4.5 and 7.0 days of development. In other regions, EIIIB+ and EIIIA+ FNs are extensively codistributed in and around mesoderm-derived structures (somites, notochord, heart, and blood vessels), in basal laminae of endoderm and ectoderm-derived structures, as well as within the vicinity of neural crest formation and migration. We also noted that EIIIA staining overlaps with spatial patterns of distribution that have previously been described for the alpha4 integrin subunit, a component of the EIIIA receptor alpha4beta1.

Alternative Splicing↗
PubMed2006

The alpha4bbeta7-integrin is dynamically expressed on murine eosinophils and involved in eosinophil trafficking to the intestine.

BACKGROUND: Of the numerous adhesion molecules expressed by eosinophils, the alpha4-integrin has been identified as critically involved in eosinophil trafficking in the lung. Most studies have focused on the role of the alpha4beta1-adhesion complex, but eosinophils also express the alpha4beta7-integrin complex. OBJECTIVE: To investigate the role of alpha4beta7, by assessing its membrane expression on eosinophils from different compartments using allergen-challenged mice and IL-4/IL-5 bi-transgenic mice. In addition, we aim to determine the impact of beta7-integrin deficiency on eosinophil recruitment to the lungs and intestine in specific experimental allergic models. RESULTS: Evaluation of alpha4beta7 expression on bronchoalveolar lavage fluid (BALF) and lung tissue eosinophils revealed a down-regulation of this integrin as eosinophils migrate through the lungs. Indeed eosinophils isolated from the BALF and lung of allergic mice had low expression of the alpha4beta7-complex. While expression of the alpha4-chain remained unchanged, a significant decrease in beta7-surface expression was observed. Intestinal eosinophils, isolated from Peyer's patches, also displayed a down-regulation of the alpha4beta7-integrin, albeit only modest. In contrast, circulating eosinophils, isolated from the blood and spleen, expressed high levels of the alpha4beta7-integrin. However, eosinophil trafficking into the lungs of beta7-integrin-deficient mice was not significantly impaired in response to respiratory allergen challenges. In contrast, beta7-deficient mice had impaired eosinophil recruitment to the intestine. CONCLUSION: Taken together, these results identify differential expression of the alpha4beta7-integrin on eosinophils and its critical role in regulating eosinophil responses in the intestine.

Animals↗
PubMed2005

RUNX3 regulates the activity of the CD11a and CD49d integrin gene promoters.

The leukocyte integrins CD11a/CD18 (LFA-1, alphaLbeta2) and CD49d (VLA-4, alpha4beta1, alpha4beta7) mediate leukocyte transendothelial migration during immune and inflammatory responses and provides co-stimulatory signals for the activation of T lymphocytes. Our previous studies demonstrate that the CD11a gene promoter directs CD11a/CD18 integrin expression, and it depends on two overlapping sequences within the MS7 element, RUNX-110 and CEBP-100, which are recognized by RUNX and C/EBP transcription factor families, respectively. Recognition of MS7 differs in lymphoid (RUNX) and myeloid (C/EBP and RUNX) cells and its in vivo occupancy is regulated in a competitive and differentiation-dependent manner. The functional relevance of these elements are illustrated by the fact that RUNX3 overexpression leads to enhanced CD11a/CD18 levels, whereas RUNX1-ETO-expressing cells exhibit a weak/absent CD11a/CD18 integrin cell surface expression. We now provide evidence that RUNX3 also transactivates the CD49d gene promoter, and that the increased expression of CD49d mRNA and CD49d integrins on mature monocyte-derived dendritic cells correlates with an up-regulation of RUNX3 mRNA. The regulation of CD49d and CD11a integrins by RUNX3 could potentially contribute to the enhancement of transendothelial migration, antigen presentation and T cell stimulatory capabilities of mature dendritic cells.

Base Sequence↗