PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Integrin alpha2”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 505 records · Page 28Linked to original sources
PubMed2001

Molecular and genetic basis for thrombasthenic thrombopathia in otterhounds.

OBJECTIVES: To determine the molecular and genetic basis for thrombasthenic thrombopathia in Otterhounds and establish whether the defect would be best classified as type-I Glanzmann's thrombasthenia. ANIMALS: 57 dogs, including 13 affected Otterhounds, 23 carrier Otterhounds, 17 unaffected Otterhounds, and 4 clinically normal unrelated dogs of other breeds. PROCEDURE: Functional (platelet aggregation, clot retraction, buccal mucosa bleeding time) and biochemical (electrophoresis, flow cytometry, fibrinogen content) analyses were conducted. In addition, first-strand cDNA synthesis from platelet total RNA was performed. Exons of the genes encoding for glycoproteins (GP) IIb and IIIa were amplified in overlapping fashion. The resulting products were excised from agarose gels and sequenced. The sequences obtained were compared with known cDNA sequences for canine GPIIb and GPIIIa. RESULTS: A single nucleotide change at position G1193 (1100) was detected in exon 12 of the gene encoding for platelet GPIIb in 2 affected Otterhounds. Carrier Otterhounds were heterozygous at this position, and 2 unaffected Otterhounds were unchanged. This nucleotide change would result in substitution of histidine for aspartic acid at position 398 (367) within the third calcium-binding domain of GPIIb. CONCLUSIONS AND CLINICAL RELEVANCE: These studies suggest that thrombasthenic thrombopathia of Otterhounds is homologous phenotypically and has a similar molecular basis to type-I Glanzmann's thrombasthenia in humans.

Amino Acid Sequence↗
PubMed1990

Sequence analysis of monoclonal antibodies derived from a patient with idiopathic thrombocytopenic purpura.

Autoantibodies directed at the platelet membrane glycoprotein Ib (GPIb) can mediate a severe form of idiopathic thrombocytopenic purpura (ITP). The platelet-specific antibody from plasma of one patient (DM) with this form of ITP displays a public idiotype termed DMId. The DMId idiotype has been found in the plasma of several patients with ITP, usually in association with GPIb-specific autoantibodies. As a step in the understanding of the molecular genetics of this form of ITP we have determined the nucleotide sequences of expressed V region genes selected from a panel of five human lymphoblastoid cell lines derived from patient DM. Two of the lines secreted antibodies that bound GPIb, and three of the lines secreted antibodies that expressed DMId. The H chain sequences of the DMId-positive antibodies and of one of the GPIb-binding antibodies belong to the VH4 family. The second GPIb-binding antibody belongs to the VH1 family. All have multiple substitutions from previously published sequences giving these antibodies the appearance of having been antigen driven. These results are consistent with the hypothesis that autoantibodies in ITP arise from a "normal" immune response inappropriately directed at platelet antigens. Further, our results suggest that VH4 gene segments may be recruited preferentially into the DMId-positive, GPIb-specific autoantibody response.

Amino Acid Sequence↗
PubMed1990

Mechanistic aspects of cellular interactions with artificial dialyzer membrane surfaces.

The platelet adhesion on adhesive protein-coated surfaces was significantly reduced by the addition of the synthetic tetrapeptide, RGDS (Arg-Gly-Asp-Ser), which was identified as the common amino acid sequence of adhesive site of adhesive proteins. The inhibitory effect was also observed for leukocyte(WBC) in complement-inactivated serum. No significant effect was observed for WBC in complement-activated serum. These indicate that the RGDS ligand-receptor mechanism operates on adhesive protein-adsorbed surfaces for both cellular systems and that activated complement factor (C3b)-membrane receptor (CR3) interaction operates for WBC as the complement is activated.

Amino Acid Sequence↗
PubMed1998

Binding of the alpha 2 integrin I domain to extracellular matrix ligands: structural and mechanistic differences between collagen and laminin binding.

The alpha 2 beta 1 integrin functions as a cell surface receptor for collagen on some cells and as both a collagen and laminin receptor on a more restricted subset of cell types including endothelial and epithelial cells. The alpha 2 integrin subunit I domain binds collagen in a divalent cation-dependent manner. In contrast, I domain binding to laminin occurs via both divalent cation-dependent and -independent mechanisms. Saturable binding was observed in the presence of either Mn2+ or EDTA, although the extent of binding in Mn2+ was twice that observed in EDTA. Half-maximal binding occurred at about 22 nM I domain in either case. Whereas laminin binding was significantly enhanced by Mn2+, with half-maximal binding occurring at 1.9 mM Mn2+, Mg2+ was much less effective. Deletion of the N-terminal 35 residues of the I domain, including the DXSXS portion of the MIDAS motif, caused a significant diminution of laminin binding activity. Laminin binding by the I domain was significantly inhibited by the alpha 2 beta 1 function-blocking antibody 6F1 in the presence of either EDTA or Mn2+. The non-function-blocking antibody 12F1 had no effect. In contrast to the binding of the alpha 2 integrin I domain to collagen, the laminin binding activity of the I domain was not enhanced by the addition of the first EF hand motif of the integrin.

Antibodies, Monoclonal↗
PubMed2001

Cutting edge: the mouse NK cell-associated antigen recognized by DX5 monoclonal antibody is CD49b (alpha 2 integrin, very late antigen-2).

DX5 mAb is a useful reagent because it stains NK cells from all mouse strains examined. We have identified the molecule recognized by DX5 mAb by using a retrovirus-mediated expression cloning system. A 5-kb cDNA encoding a protein that is reactive with the DX5 mAb was isolated from a NK cell cDNA library, and this molecule was identical with CD49b (very late Ag-2, alpha(2) integrin). The DX5 mAb reacted with transfectants expressing CD49b, and binding of DX5 to the NK cells and CD49b transfectants was blocked in the presence of other anti-CD49b mAbs. When NK1.1(+) NK cells were cultured with IL-2, they progressively lost reactivity with DX5 mAb as a consequence of cellular proliferation. Cytotoxicity mediated by the DX5(+) NK cells was dramatically higher as compared with DX5(-) NK cells. Therefore, DX5 mAb recognizes CD49b and can be used to define functionally distinct subsets of NK cells.

Animals↗
PubMed2002

NK T cell precursors exhibit differential cytokine regulation and require Itk for efficient maturation.

NK T cells are a lymphocyte lineage that is selected by CD1d and is characterized by the ability to rapidly secrete large amounts of both IFN-gamma and IL-4 after TCR stimulation. Using reactivity to CD1d tetramers to define presumptive NK T cells, several NK T cell progenitor populations were characterized based upon NK marker expression and CD4 vs CD8 expression. The earliest populations were found to be negative for NK markers and could proliferate to IL-7, while mature NK T cells did not. The NK1.1(-) NK T cell progenitors were capable of up-regulating NK1.1 when transferred in vivo. Upon stimulation, the NK1.1(-) populations secrete IL-4, but little IFN-gamma. As the cells mature and up-regulate NK1.1, they acquire the ability to secrete IFN-gamma. Finally, the Tec family tyrosine kinase Itk is necessary for optimal NK1.1 up-regulation and hence final maturation of NK T cells. The itk(-/-) mice also display a progressive decrease in NK T cells in older animals, suggesting a further role in peripheral maintenance.

Animals↗
PubMed2005

DX5/CD49b-positive T cells are not synonymous with CD1d-dependent NKT cells.

NKT cells are typically defined as CD1d-dependent T cells that carry an invariant TCR alpha-chain and produce high levels of cytokines. Traditionally, these cells were defined as NK1.1+ T cells, although only a few mouse strains express the NK1.1 molecule. A popular alternative marker for NKT cells has been DX5, an Ab that detects the CD49b integrin, expressed by most NK cells and a subset of T cells that resemble NKT cells. Interpretation of studies using DX5 as an NKT cell marker depends on how well DX5 defines NKT cells. Using a range of DX5 and other anti-CD49b Abs, we reveal major differences in reactivity depending on which Ab and which fluorochrome are used. The brightest, PE-conjugated reagents revealed that while most CD1d-dependent NKT cells expressed CD49b, they represented only a minority of CD49b+ T cells. Furthermore, CD49b+ T cell numbers were near normal in CD1d-/- mice that are completely deficient for NKT cells. CD1d tetramer- CD49b+ T cells differ from NKT cells by their activation and memory marker expression, tissue distribution, and CD4/CD8 coreceptor profile. Interestingly, both NKT cells and CD1d tetramer- CD49b+ T cells produce cytokines, but the latter are clearly biased toward Th1-type cytokines, in contrast to NKT cells that produce both Th1 and Th2 cytokines. Finally, we demonstrate that expression of CD49b by NKT cells does not dramatically alter with age, contrasting with earlier reports proposing DX5 as a maturation marker for NKT cells. In summary, our data demonstrate that DX5/CD49b is a poor marker for identifying CD1d-dependent NKT cells.

Animals↗
PubMed2006

Functional specialization of memory Th cells revealed by expression of integrin CD49b.

Infection or immunization induces heterogeneous memory T cell subsets, but their origin and protective value against infection are unclear. In this study, we report the functional characterization of two memory Th subsets, defined by expression of integrin CD49b. Stable CD49b expression is induced in up to one-half of all memory Th cells. More importantly, the CD49b- and CD49b+ subsets display distinct helper activities, typified by the production of IL-10 and TNF-alpha, respectively. Although the inflammatory properties of the CD49b+ subset are protective against intracellular bacterial infection, they are associated with immunopathology in acute viral infection. Modulation of the CD49b-defined memory Th subsets may provide infection type-specific interventions, where either enhancement of the inflammatory response or reduction of immunopathology is essential.

Animals↗
PubMed2006

Immature dendritic cells suppress collagen-induced arthritis by in vivo expansion of CD49b+ regulatory T cells.

Dendritic cells (DCs) are specialized APCs with an important role in the initiation and regulation of immune responses. Immature DCs (iDCs) reportedly mediate tolerance in the absence of maturation/inflammatory stimuli, presumably by the induction of regulatory T cells. In this study, we show for the first time that repetitive iDC injections trigger the expansion of a novel regulatory population with high immunomodulatory properties, able to protect mice from collagen-induced arthritis. These regulatory T cells are characterized by the expression of the CD49b molecule and correspond to a CD4+ alpha-galactosylceramide/CD1d-nonrestricted T cell population producing IL-10. Adoptive transfer of < 10(5) TCRbeta+ CD49b+ cells isolated from the liver of iDCs-vaccinated mice, conferred a complete protection against arthritis. This protection was associated with an attenuation of the B and T cell response associated with a local secretion of IL-10. Thus, together these data demonstrate that iDCs can expand and activate a novel regulatory population of CD49b+ T cells, with high immunosuppressive potential able to mediate protection against a systemic autoimmune disease.

Adoptive Transfer↗
PubMed1999

A point mutation Thr(799)Met on the alpha(2) integrin leads to the formation of new human platelet alloantigen Sit(a) and affects collagen-induced aggregation.

A new platelet-specific alloantigen, termed Sit(a), was identified in a severe case of neonatal alloimmune thrombocytopenia. The Sit(a) alloantigen is of low frequency (1/400) in the German population. Immunochemical studies demonstrated that the Sit(a) epitopes reside on platelet glycoprotein (GP) Ia. Nucleotide sequence analysis of GPIa cDNA derived from Sit(a)-positive platelets showed C(2531)-->T(2531) point mutation, resulting in Thr(799)Met dimorphism. Analysis of genomic DNA from 22 Sit(a)-negative normal individuals showed that the Thr(799) is encoded by ACG(2532) (90.9%) or ACA(2532) (9.1%). To establish a DNA typing technique, we elucidated the organization of the GPIa gene adjacent to the polymorphic bases. The introns (421 bp and 1.2 kb) encompass a 142-bp exon with the 2 polymorphic bases 2531 and 2532. Polymerase chain reaction-restriction fragment length polymorphism analysis on DNA derived from 100 donors using the restriction enzyme Mae III showed that the Met(799) form of GPIa is restricted to Sit(a) (+) phenotype. Analysis of stable Chinese hamster ovary transfectants expressing allele-specific recombinant forms of GPIa showed that anti-Sit(a) exclusively reacted with the Glu(505)Met(799), but not with the Glu(505)Thr(799) and the Lys(505)Thr(799) isoforms. In contrast, anti-Br(a) (HPA-5b) only recognized the Lys(505)Thr(799) form, whereas anti-Br(b) (HPA-5a) reacted with both Glu(505)Thr(799) and Glu(505)Met(799) isoforms. These results demonstrated that the Met(799) is responsible for formation of the Sit(a) alloantigenic determinants, whereas amino acid 505 (Lys or Glu) specifically controls the expression of Br(a) and Br(b) epitopes, respectively. Platelet aggregation responses of Sit(a) (+) individuals were diminished in response to collagen, indicating that the Thr(799)Met mutation affects the function of the GPIa/IIa complex.

Animals↗
PubMed2000

Monitoring of aspirin (ASA) pharmacodynamics with the platelet function analyzer PFA-100.

BACKGROUND: Anti-platelet drug therapy is currently performed without monitoring, because the established method of platelet aggregometry is cumbersome. The recently developed platelet function analyzer PFA-100 measures shear stress dependent, collagen epinephrine (CEPI) and collagen adenosine diphosphate (CADP) induced platelet plug formation. As the PFA-100 provides a valuable tool to detect patients with platelet dysfunction more efficiently and cost-effectively than aggregometry, we investigated its potential to monitor the efficacy of aspirin treatment. METHODS: All healthy volunteers (n = 10) received a fractionated infusion of L-aspirin to establish individual dose-response curves. Further, in a randomized, double-blind, placebo controlled two-way cross over study the same volunteers received either 50 or 100 mg aspirin/day p.o. for a period of 11 days to determine the day-to-day variability CEPI induced closure time (CT) under constant intake of low dose aspirin, and to compare the efficacy of those two doses. RESULTS: Intra- and intersubject variability of CEPI-CT averaged 9% and 22%, respectively. Seven volunteers exceeded the maximum of CEPI-CT (>300 s) already after infusion of 100 mg L-aspirin. Intake of 100 mg of aspirin elicited a more rapid onset of effect than 50 mg, which was only significant on days 3 and 4 of aspirin intake. The aspirin induced CEPI-CT prolongation correlated positively with basal CEPI-CT values (r = 0.86; p = 0.001) and were strongly dependent on von Willebrand Factor levels (r = -0.9; p = 0.001). CONCLUSION: Thus, the PFA-100 system appears suitable to demonstrate an aspirin-induced platelet effect in a longitudinal study, and may be adequate to monitor a patient's compliance. However, prospective trials have to be conducted to demonstrate whether the EPI-CT achieved under ASA-intake has predictive value for cardiovascular outcome.

Adenosine Diphosphate↗
PubMed2001

Down-regulation of E-cadherin gene expression by collagen type I and type III in pancreatic cancer cell lines.

E-cadherin-mediated cell-cell adhesion is reduced in epithelial tumors, which is thought to be a prerequisite to acquire invasive properties. We observed that several pancreatic carcinoma cell lines with high metastatic potential expressed normal levels of E-cadherin and possessed functional E-cadherin/catenin adhesion complexes. When the cell lines PANC-1, BxPC-3, and PaTu8988s were cultured either on type I or type III collagen, E-cadherin gene expression was repressed, and E-cadherin and catenin protein concentrations were reduced. In contrast, growth on fibronectin and collagen type IV had no influence. Collagen type I- or type III-dependent reduction of E-cadherin expression led to decreased cell-cell adhesion, increased proliferation, and migratory activity as well as morphological transformation. Overexpression of activated c-Src in PANC-1 cells mimicked collagen-induced E-cadherin down-regulation and changed the elevated cell proliferation and migration. Conversely, treatment of cells with the Src-inhibitors PP1 or herbimycin A resulted in complete suppression of collagen type I-induced E-cadherin decrease. Our data demonstrate that specific collagens are able to promote metastatic behavior by down-regulation of E-cadherin gene expression in a Src-kinase-dependent manner. This points toward a novel mechanism for substrate-dependent signaling and underlines the significance of extracellular matrix environment for tumor growth and invasiveness.

Antigens, CD↗
PubMed1998

[The study of platelet function in patients with chronic pulmonary heart disease].

OBJECTIVE: To study the platelet function in patients with chronic pulmonary heart disease. METHOD: Subjects were divided into three groups (cor pulmonale exacerbation, cor pulmonale remission stage and normal control). Platelet adhesion rate (PAdT), platelet aggregation rate(PAgT), alpha-granule membrane protein (GMP-140) and glycoproteinII were measured by radioimmunoassay, flow cytometry and other methods. RESULT: In cor pulmonale exacerbation, the values of PAdT, PAgT, GMP-140 and GPII were31% +/- 16%, 14% +/- 8%, 190 +/- 49 molecule/platelet and 145% +/- 36% respectively. In cor pulmonale remission stage, the values were 33% +/- 13%, 38% +/- 16%, 178 +/- 33 molecule/platelet and 137% +/- 48% respectively. These findings showed that the values of PAdT, GMP-140 and GPII in cor pulmonale exacerbation were markedly increased, whereas PAgT was significantly reduced. However, PAdT, PAgT, GMP-140 and GPII in remission stage were all higher than that of normal group. CONCLUSION: In vivo platelet activation is indeed present in patients with chronic pulmonary heart disease.

Aged↗
PubMedDate not supplied

[Familial occurrence of Glanzmann thrombasthenia].

Glanzmann's thrombasthenia, known also as Glanzmann's disease, is an autosomally inherited hemorrhagic disease with unique abnormalities of platelet functions. Authors present a large family in which Glanzmann's disease was diagnosed in the father and two sons. An analysis of platelet membranes enabled diagnosis of Glanzmann's thrombasthenia type II. A decrease in clot contractibility, fibrinogen binding to blood platelets, and decreased glycoprotein IIb and IIIa levels with marked impairment of GP IIb and IIIa complexes formation were characteristic for affected family members. One daughter died 8 days after birth with the symptoms of hemorrhagic diathesis. Mother and remaining three sons are healthy without the signs of Glanzmann's disease.

Adolescent↗
PubMed2003

[Association of the polymorphism of platelet membrane glycoprotein I a gene with myocardial infarction].

OBJECTIVE: Platelet membrane glycoprotein (GP) Ia/IIa complex is the major collagen receptor on platelets. Platelet activation by GP Ia/ IIa dependent adhesion leads to cellular events that catalyze prothrombin conversion and fibrin clot formation. Correlation between the polymorphism of platelet membrane GP Ia gene and myocardial infarction (MI) was explored. METHODS: A total of 137 patient s with myocardial infarction and 175 controls with no history of coronary heart disease, thrombogenic and hemorrhagenic diseases were studied by case-control. Platelet GP I a gene 807 C/T polymorphisms were checked by polymerase chain reaction-sequence specific primers. RESULTS: There were significant differences in the distribution of T and C alleles between MI and control groups (T:42.70% vs 32.00%, C:57.30% vs 68.00%, P<0.001). No matter among all subjects or among subjects aged <or= 60 years, the prevalence of genotypes (TT+TC) in MI group was significantly higher than that in control group [in all subjects; 69.34% vs 51.43%, P<0.005, odds ratio(OR)=2.14, 95% CI: 1.34-3.41; in subjects aged <or= 60 years; 75.90% vs 51. 52%, P<0.005, OR=2.96,95% CI 1.58-5.55]. Platelet GP Ia T allele was significantly associated with MI by multiple logistic regression (OR=4.96, 95% CI:2.55-10.90). CONCLUSION: The above data suggest that there is a strong association between the presence of GP Ia T allele and MI. T allele ca n be a marker of genetic susceptibility to MI. These need to be substantiated by a large scale and prospective study.

Aged↗