Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Chain Migration”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 1,081 records · Page 60Linked to original sources
PubMed2005

IL-15 induces mast cell migration via a pertussis toxin-sensitive receptor.

IL-15 induces proliferation, inhibits apoptosis and increases IL-4 production in murine mast cells. There is evidence that these activities are mediated via the uncharacterised receptor, IL-15R-X, rather than the classical three-chain IL-15 receptor. Effects of IL-15 on important aspects of mast cell biology, such as migration and degranulation, are unknown. We report that IL-15 induces migration of murine and human mast cells in a dose-dependent and biphasic manner, with peaks of migration occurring at approximately 10(-15) and approximately 10(-9) M. The potency of the response was similar to that induced by other well-established mast cell chemoattractants. Competition assays performed with murine and human mast cells indicate that both peaks of migration are due to chemotaxis. Pre-treatment of cells with pertussis toxin (PTX), a guanine nucleotide-binding regulatory protein (G-protein) inhibitor, resulted in complete inhibition of murine mast cell migration at approximately 10(-15) M IL-15, and human mast cell migration at approximately 10(-15) and approximately 10(-9) M. This demonstrates that murine and human mast cells express a PTX-sensitive receptor, activated in response to IL-15. Additionally, IL-15 did not induce degranulation in murine mast cells. Locally-produced IL-15 may contribute to mast cell recruitment during inflammatory responses, thereby acting as a linking cytokine between innate and adaptive arms of the immune system.

Animals↗
PubMed1995

Drosophila nonmuscle myosin II is required for rapid cytoplasmic transport during oogenesis and for axial nuclear migration in early embryos.

The X-linked Drosophila gene spaghetti squash (sqh) encodes the regulatory light chain of nonmuscle myosin II. To assess the requirement for myosin II in oogenesis and early embryogenesis, we induced homozygous germline clones of the hypomorphic mutation sqh1 in otherwise heterozygous mothers. Developing oocytes in such sqh1 germline clones often failed to attain full size due to a defect in 'dumping', the rapid phase of cytoplasmic transport from nurse cells. In contrast to other dumpless mutants described to date, sqh1 egg chambers showed no evidence of ring canal obstruction, and no obvious alteration in the actin network. However the distribution of myosin II was abnormal. We conclude that the molecular motor responsible for cytoplasmic dumping is supplied largely, if not exclusively, by nurse cell myosin II and we suggest that regulation of myosin activity is one means by which cytoplasmic transport may be controlled during oocyte development. The eggs resulting from sqh1 clones, though smaller than normal, began development but exhibited an early defect in axial migration of cleavage nuclei towards the posterior pole of the embryo, in a similar manner to that seen in early cleavage eggs in which the actin cytoskeleton is disrupted. Thus both nurse cell dumping and axial migration require a maternally supplied myosin II.

Actins↗
PubMed1997

The A10 cell line: a model for neonatal, neointimal, or differentiated vascular smooth muscle cells?

OBJECTIVES: The A10 cell line was derived from the thoracic aorta of embryonic rat and is a commonly used model of vascular smooth muscle cells (VSMC). Despite its wide use this cell line has not been well characterized. This is especially important in light of recent evidence of phenotypically distinct cell populations isolated from rat vascular tissue. Therefore, the present study was undertaken to confirm the VSMC nature of A10 cells and to investigate whether these cells particularly resemble adult, neonatal, or neointimal rat VSMC. METHODS: A variety of defining characteristics were used that included immunofluorescent analysis for smooth muscle alpha-actin, smooth and non-muscle myosin heavy chains, desmin and vimentin; Western analysis for smooth muscle and non-muscle myosin heavy chains; mRNA analysis for smooth muscle myosin heavy chain, calponin, SM22 alpha, tropoelastin and PDGF-B peptide; and functional assays of cell migration, proliferation and agonist induced intracellular Ca transients. RESULTS: A10 cells expressed smooth muscle alpha-actin, SM22 alpha, smooth muscle calponin and vimentin, characteristic of in vivo rat VSMCs; however they also resembled de-differentiated smooth muscle cells in that they expressed non-muscle myosin rather than smooth muscle myosin heavy chain. A10 cells resembled cultured rat neonatal smooth muscle cells ("pup cells") in that they had an epithelioid shape and lacked functional PDGF-alpha receptors: however they did not express PDGF-B mRNA or proliferate in low serum containing medium as do neonatal cells. A10 cells had several characteristics in common with neointimal cells including the expression of alpha-actin, vimentin, and non-muscle myosin and the lack of expression of PDGF-B mRNA as well as the ability to migrate in response to PDGF-BB. CONCLUSION: In conclusion, A10 cells are nondifferentiated VSMC that differ from neonatal but bear significant resemblance to neointimal cells.

Actins↗
PubMed2006

Distribution of laminins in the developing human eye.

PURPOSE: To examine the distribution of laminin (Ln) chains in basement membranes (BMs) of the human cornea, lens, and retina in fetal development. METHODS: Ten fetal eyes (9-20 weeks of gestation [wg]) were serially sectioned and treated with specific antibodies against the Ln-alpha1, -alpha2, -alpha3, -alpha4, -alpha5, -beta1, -beta2, -beta3, and -gamma1 chains. RESULTS: The BM of the corneal epithelium was reactive for Ln-alpha3, -alpha5, -beta1, and beta3 chains through all ages, whereas the Ln-alpha1 chain was present at 9 to 12 wg and the Ln-alpha4 chain from 10 wg. The Descemet's membrane (DM) was labeled with the Ln-alpha1 and -alpha4 chains at 10 to 17 wg, the Ln-alpha5 chain from 10 wg, the Ln-beta1 chain at 11 to 17 wg, and the Ln-beta3 chain from 17 wg. The Ln-alpha1, alpha5, -beta1, and -beta2 chains were present in the lens capsule and the internal limiting membrane (ILM) through all ages. The Bruch's membrane (BrM) was immunoreactive for the Ln-alpha3, alpha4, -alpha5, -beta1, and -beta2 chains through all ages, whereas the Ln-alpha1 chain was absent from 20 wg onward. The Ln-alpha2 chain was not detected in the eye, but it was present in the extraocular muscles. CONCLUSIONS: BMs play an important role during morphogenesis, in that they influence cell proliferation, migration, and tissue differentiation. Lns are the major noncollagenous component of BMs. The presence of four different alpha chains, three beta chains, and one gamma chain of Ln in the eye reveals a high degree of complexity from the early stages of development and suggests an important role for the different Ln chains in human ocular differentiation.

Basement Membrane↗
PubMed1992

Involvement of beta 2-integrins in the migration of human natural killer cells.

Human large granular lymphocytes with the NK cell phenotype (CD16+ or CD56+CD3-) were greatly enriched among the cells which migrated spontaneously through untreated or albumin-coated, 3-microns pore size polycarbonate filters for 1 to 8 h. Three days of rIL-2 treatment (300 IU/ml) and 3 to 5 wk of rIL-2 treatment (100 IU/ml) generated a 2.7 +/- 0.9-fold and 5.6 +/- 0.8-fold increase in cell migration, respectively. The adhesion and subsequent migration of freshly isolated NK cells was mainly mediated by CD11b/CD18, because migration could be inhibited by 80 +/- 8% anti-CD11b (Mac-1) antibodies but not with antibodies against CD11a (LFA-1) or CD11c (p150,95), the other alpha-chains of the beta 2-integrins. After rIL-2 activation, however, CD11a/CD18 was the major receptor utilized in migration, inasmuch as anti-CD11a antibody caused a 69 +/- 8% reduction in the number of migrated cells. Anti-CD11b antibody decreased migration by 43 +/- 12%, and together these antibodies inhibited migration by 82 +/- 7%. Anti-CD11a alone did not have any effect on adhesion, but CD11a/CD18 cooperated in the adhesion because anti-CD11b decreased adhesion by 40 +/- 11% and together these antibodies inhibited adhesion by 74 +/- 6%. The ability of large granular lymphocytes to rapidly utilize beta 2-integrins and unidentified ubiquitous ligands for binding and migration may be significant for their capacity to function in the first line of immune defense under highly variable conditions.

Antibodies, Monoclonal↗
PubMed2000

Cancer of the vagina: Laminin-5gamma2 chain expression and prognosis.

The purpose of this experiment was to investigate the expression and the prognostic impact of the gamma2 subchain of laminin-5 in vaginal malignancies. The outcome of the rare disease primary carcinoma of the vagina is poor and little is known about prognostic markers. The gamma2 chain of laminin-5, an epithelial basement membrane protein, is thought to play a crucial role in tumor cell adhesion, migration, and proliferation, and may thus be an additive potential marker. Archival, paraffin-embedded sections were stained immunohistochemically with an antibody against the gamma2 chain of human laminin-5 protein. The material consisted of 59 cases of primary vaginal malignancies, subdivided into short- and long-time survivors. All invasive malignancies of epithelial origin were positively stained with the antibody against the gamma2 chain. High expression of the gamma2 chain correlated significantly in an univariate analysis with short-time survival (P = 0.041), but in the multivariate analysis only age and tumor size were independent prognostic factors. A significant intercorrelation between large tumors and high gamma2 chain immunoreactivity was found (P = 0.003). These results indicate that laminin-5gamma2 subchain expression in primary vaginal carcinomas is of prognostic impact. However, in a multivariate analysis only patient age and tumor size had independent prognostic value.

Journal Article↗
PubMed1999

Molecular analysis of the carboxy terminus of the beta and gamma subunits of the epithelial sodium channel in patients with end-stage renal disease.

BACKGROUND: Mutations in the carboxy termini of the beta subunit (hbetaENaC) and the gamma subunit (hgammaENaC) of the human epithelial sodium channel have been identified in patients with Liddle syndrome. Moreover polymorphisms have been described in these genes, the clinical relevance of which for progression to end-stage renal disease (ESRD) is unknown. We, therefore, have screened ESRD patients for putative variants of these genes. METHODS: We investigated 256 chronic hemodialysis patients, including 123 patients with a history of hypertension as a cause of ESRD. Screening for mutations in the carboxy termini of hbetaENaC and hgammaENaC was accomplished by polymerase chain reaction amplification followed by single-strand conformation polymorphism analysis. RESULTS: In 231 patients single-strand conformation polymorphism analysis of the polymerase chain reaction fragments of the hbetaENaC and hgammaENaC genes showed a similar migration pattern as compared with negative control subjects. In 25 patients a band shift was observed. However, sequence analysis in all these patients revealed wild-type sequence. CONCLUSIONS: The present study demonstrates the absence of genetic variants in the carboxy terminus of the hbetaENaC and hgammaENaC genes in Austrian patients with ESRD maintained on chronic hemodialysis treatment. Thus, mutations in these genes are unlikely to be associated with ESRD.

DNA Primers↗
PubMed2004

PAI-1 expression is required for epithelial cell migration in two distinct phases of in vitro wound repair.

Several proteases and their specific inhibitors modulate the interdependent processes of cell migration and matrix proteolysis as part of the global program of trauma repair. Expression of plasminogen activator inhibitor type-1 (PAI-1), a serine protease inhibitor (SERPIN) important in the control of barrier proteolysis and cell-to-matrix adhesion, for example, is spatially-temporally regulated following epithelial denudation injury in vitro as well as in vivo. PAI-1 mRNA/protein synthesis was induced early after epidermal monolayer scraping and restricted to keratinocytes comprising the motile cohort closely recapitulating, thereby, similar events during cutaneous healing. The time course of PAI-1 promoter-driven PAI-1-GFP fusion "reporter" expression in wound-juxtaposed cells approximated that of the endogenous PAI-1 gene confirming the location-specificity of gene regulation in this model. ERK activation was evident within 5 min after injury and particularly prominent in cells residing at the scrape-edge (suggesting a possible role in PAI-1 induction and/or the motile response) as was myosin light chain (MLC) phosphorylation. Indeed, MEK blockade with PD98059 or U0126 attenuated keratinocyte migration (by > or =60%), as did transient transfection of a dominant-negative ERK1 construct (40% decrease in monolayer repair), and completely inhibited PAI-1 transcript expression. Anti-sense down-regulation of PAI-1 synthesis (by 80-85%), or addition of PAI-1 neutralizing antibodies also inhibited injury site closure over a 24 h period establishing that PAI-1 was required for efficient long-term planar motility in this system. PAI-1 anti-sense transfection or actinomycin D transcriptional blockade, in contrast, did not affect the initial migratory response suggesting that residual PAI-1 protein levels (at least in transfectant cells and actinomycin D-treated cultures) may be sufficient to support early cell movement. Pharmacologic inhibition of keratinocyte MEK signaling effectively ablated scrape-induced PAI-1 mRNA expression but failed to attenuate wound-associated increases in cellular PAI-1 protein levels soon after monolayer injury. Collectively, these data suggest that basal PAI-1 transcripts may be mobilized for initial PAI-1 synthesis and, perhaps, the early motile response while maintenance of the normal rate of migration requires the prolonged PAI-1 expression that typically accompanies the repair response. To assess this possibility, scrape site closure studies were designed using keratinocytes isolated from PAI-1-/- mice. PAI-1-/- keratinocytes, in fact, had a significant wound healing defect evident even within the first 6 h following monolayer denudation injury. Addition of active PAI-1 protein to PAI-/- keratinocytes rescued the migratory phenotype that that approximating wild-type cells. These findings validate use of the present keratinocyte model to investigate injury-related controls on PAI-1 gene regulation and, collectively, implicate participation of PAI-1 in two distinct phases of epidermal wound repair.

Animals↗
PubMed1981

Characterization of the defect in activation of factor IX Chapel Hill by human factor XIa.

Factor IXChapel Hill (Factor IXCH), an abnormal Factor IX molecule isolated from the plasma of a patient with mild hemophilia B, has previously been shown to exhibit delayed activation by Factor XIa and calcium. In this study, we have found that Factor IXCH is cleaved upon incubation with human Factor XIa and calcium; however, cleavage of this protein is not observed by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis under nonreducing conditions. Under reducing conditions, the rate of disappearance of the zymogen parallels both the appearance of the heavy chain and the generation of clotting activity. In addition, a protein band that migrates with an apparent molecular weight of 45,000 also increases in parallel with clotting activity. Factor IXCH and normal Factor IX (Factor IXN), after incubation with Factor XIa and calcium, were subjected to amino terminal sequence analysis. Activated Factor IXN is cleaved at an arginine-alanine (Arg-Ala) bond and an arginine-valine (Arg-Val) bond as demonstrated by formation of the three amino terminal sequences corresponding to the amino terminal of the light chain, heavy chain, and activation peptide. However, activated Factor IXCH has only two amino terminal sequences, corresponding to the original amino terminal sequence and the heavy chain (formed by cleavage at the Arg-Val bond). It is concluded that the major defect in Factor IXCH is the inability of Factor XIa to cleave the Arg-Ala bond at a significant rate. The rate of formation of clotting activity of Factor IXCH is approximately 60% of the rate of formation of clotting activity of Factor IXN. The specific clotting activity of activated Factor IXCH is between 20 and 33% of activated Factor IXN.

Amino Acid Sequence↗
PubMed1999

Proteoglycans on normal and migrating human corneal endothelium.

Proteoglycans are of fundamental importance to the normal functioning of the cornea. They consist of a core protein to which one or more glycosaminoglycan chains are attached. Cell surface proteoglycans are known to mediate many aspects of cell behaviour including cell adhesion, control of extracellular matrix deposition, cell proliferation, cell migration, leukocyte adhesion and modulation of growth factor activity. This paper describes the first investigation into the distribution and function of the three main classes of proteoglycans on human corneal endothelium. Immuno-gold labelling techniques were used at the light, scanning and transmission electron microscope level to localise heparan sulphate, chondroitin sulphate and keratan sulphate proteoglycans on human corneal endothelium. Human corneas were freeze-wounded and kept in organ culture for 3 days in order to study the distribution of proteoglycans on migrating corneal endothelium. An Optimas image analysis system was used to quantify the change in proteoglycan labelling during cell migration. Labelling for chondroitin sulphate and heparan sulphate was at very low levels on normal corneal endothelium while keratan sulphate labelling was at high levels. The wound healing experiments showed that migrating cells had increased labelling for heparan sulphate and chondroitin sulphate with greatly decreased labelling for keratan sulphate. Statistical analysis showed these changes were highly significant (P<0.001). Transmission electron microscopy revealed that chondroitin sulphate and keratan sulphate were present throughout Descemet's membrane while heparan sulphate was concentrated at the interface of Descemet's membrane and the migrating corneal endothelial cells. The pattern of occurrence of chondroitin sulphate, heparan sulphate and keratan sulphate on the human endothelium in normal and wounded cornea suggests that these proteoglycans are linked to the process of cell migration.

Cell Movement↗
PubMed1983

Characterization of the major polypeptide chains of reduced bovine thyroglobulin.

The finding that reduced 19S bovine thyroglobulin showed two major, closely migrating polypeptide bands during electrophoresis in SDS-polyacrylamide gels was presented as evidence that thyroglobulin consists of two nonidentical subunits, referred to as S and F, of approximately the same size (J. Biol. Chem. 253, 1853-1858 (1978)). It was, however, not clear whether the difference in migration rates of the two subunits was due to differences in amino acid or carbohydrate composition or a small difference in size. In this study, several physical and chemical properties of purified S and F polypeptides were investigated. Three methods revealed important differences between them. It was found by cyanogen bromide degradation that S contained one fragment (Mr approximately equal to 20 000) more than F. S eluted ahead of F by column chromatography in SDS. The sedimentation coefficient of S was found to be greater than that of F. However, the two subunits were shown to have similar amino acid and carbohydrate compositions and to be indistinguishable in their interaction with SDS. The different migration rates of S and F can therefore be explained by a small difference in size which agrees with the finding (Endocrinology 108, 1285-1292 (1981)) that a proteolytic enzyme present in commercial horseradish peroxidase can convert S into F.

Amino Acids↗
PubMed1986

The effects of new local anti-inflammatory steroids on leucocyte migration and prostanoid liberation in rats.

The local anti-inflammatory potency of steroid-21-oate esters derived from prednisolone was determined by cotton pellet granuloma bioassay. The doses which inhibited granuloma formation by 50% (ID50) were: prednisolone, 0.5 mg/pellet; methyl 20 alpha-dihydroprednisolonate, 5.8 mg/pellet; methyl 20 beta-dihydroprednisolonate, 1.2 mg/pellet; methyl 17,20 alpha-acetonidodihydroprednisolonate, 6.0 mg/pellet. When administered at these equipotent local anti-inflammatory doses, only prednisolone depressed plasma corticosterone and promoted thymus involution. Prednisolone reduced neutrophil migration into saline-soaked polyester sponges and depressed the levels of 6-keto PGF1 alpha, PGE2 and elastase in the sponge-induced inflammatory exudate. Methyl 20 alpha- and 20 beta-dihydroprednisolonate had no effect on cell migration, but depressed the levels of 6-keto PGF1 alpha and elastase. The liberation of 6-keto PGF1 alpha, PGE2 and elastase and neutrophil migration were inhibited by methyl 17,20 alpha- and beta-acetonidodihydroprednisolonate, but the effect of the beta-epimer on cell migration was transient. These data suggest that steroid acid esters which have local and topical anti-inflammatory properties exert their effect in a similar fashion to glucocorticoids with a ketol side-chain (e.g. prednisolone) with respect to liberation of prostaglandins and lysosomal enzymes. However, their effect on neutrophil migration was variable, depending on their structural features. Furthermore, the systemic effects of these new derivatives were drastically reduced indicating that they may be of potential benefit in prolonged treatment.

Animals↗
PubMed2001

Marching at the front and dragging behind: differential alphaVbeta3-integrin turnover regulates focal adhesion behavior.

Integrins are cell-substrate adhesion molecules that provide the essential link between the actin cytoskeleton and the extracellular matrix during cell migration. We have analyzed alphaVbeta3-integrin dynamics in migrating cells using a green fluorescent protein-tagged beta3-integrin chain. At the cell front, adhesion sites containing alphaVbeta3-integrin remain stationary, whereas at the rear of the cell they slide inward. The integrin fluorescence intensity within these different focal adhesions, and hence the relative integrin density, is directly related to their mobility. Integrin density is as much as threefold higher in sliding compared with stationary focal adhesions. High intracellular tension under the control of RhoA induced the formation of high-density contacts. Low-density adhesion sites were induced by Rac1 and low intracellular tension. Photobleaching experiments demonstrated a slow turnover of beta3-integrins in low-density contacts, which may account for their stationary nature. In contrast, the fast beta3-integrin turnover observed in high-density contacts suggests that their apparent sliding may be caused by a polarized renewal of focal contacts. Therefore, differential acto-myosin-dependent integrin turnover and focal adhesion densities may explain the mechanical and behavioral differences between cell adhesion sites formed at the front, and those that move in the retracting rear of migrating cells.

Cells, Cultured↗
PubMed2003

Myosin heavy chain kinase B participates in the regulation of myosin assembly into the cytoskeleton.

Myosin II plays critical roles in events such as cytokinesis, chemotactic migration, and morphological changes during multicellular development. The amoeba Dictyostelium discoideum provides a simple system for the study of this contractile protein. In this system, myosin II filament assembly is regulated by myosin heavy chain (MHC) phosphorylation in the tail region of the molecule. Earlier studies identified an alpha-kinase, MHC kinase A (MHCK A), which phosphorylates three mapped threonine residues in the myosin tail, driving myosin disassembly. Using molecular and genomic approaches, we have identified a series of related kinases in Dictyostelium. The enzyme MHCK B shares with MHCK A a domain organization that includes a highly novel catalytic domain coupled to a carboxyl-terminal WD repeat domain. We have engineered, expressed, and purified a FLAG-tagged version of the novel kinase. In the present study, we report detailed biochemical and cellular studies documenting that MHCK B plays a physiological role in the control of Dictyostelium myosin II assembly and disassembly during the vegetative life of Dictyostelium amoebae. The presented data supports a model of multiple related MHCKs in this system, with different regulatory mechanisms and pathways controlling each enzyme.

Animals↗
PubMedDate not supplied

Hypertrophic cardiomyopathy: failure to demonstrate mutations in exon 13 of the cardiac beta myosin heavy-chain gene.

Familial hypertrophic cardiomyopathy (FHCM) has been linked to the cardiac beta-myosin heavy-chain (MHC) genes on chromosome 14 (14q1), and a missense mutation within exon 13 of the beta MHC gene has been implicated in the pathogenesis of the disease. To test whether this constitutional mutation occurs somatically in the myocardium of the sporadic form of the disease, we studied seven patients with familial (n = 3) or sporadic (n = 4) hypertrophic cardiomyopathy (HCM). Amplification of exon 13 of the beta MHC from paraffin-embedded myocardium using the polymerase chain reaction (PCR) was performed and analysis of the amplified product for migration abnormalities using denaturing gradient gel electrophoresis (DGGE) and direct sequencing of the PCR product were used. Neither patients with HCM nor subjects with dilated cardiomyopathy (DCM) (n = 2) exhibited an aberration within exon 13 of the myocardial beta MHC. It is concluded that a specific beta MHC gene mutation is displayed only in a subset of patients with familial disease, thus further emphasizing the notion of genetic heterogeneity. In addition, in the sporadic form of the disease, somatically occurring mutations in this particular exon could not be demonstrated.

Base Sequence↗
PubMed1991

VLA-2 is a collagen receptor on endothelial cells.

In order to identify cell-substrate adhesion receptors on vascular endothelium, murine monoclonal antibodies (MoAb) were raised against human umbilical vein endothelial cells (HUVE). One anti-HUVE MoAb, RMAC11, identified the adhesion receptor VLA-2 as it immunoprecipitated a non-covalently linked heterodimer of 160 kD and 130 kD, which was identical to the heterodimer immunoprecipitated by the anti-VLA-2 MoAb, 12F1 and 5E8. Furthermore, proteolytic peptide maps of the VLA-2 alpha- and beta-chains were highly homologous with those of the RMAC11-recognized molecule. However, unlike other VLA-2 MoAb, RMAC11 also identified an 85 kD band which migrated to 90 kD under reducing conditions. This band was most likely a fragment of the 160 kD alpha-chain as a similar alpha-chain derived fragment has been demonstrated in the immunoprecipitates of some VLA-4 reactive monoclonals. However the possibility that this may be a novel molecule associated with VLA-2 has not been excluded. In vitro assays of HUVE adhesion to collagen types 1 and 4, laminin and fibronectin showed that RMAC11 blocked adhesion to collagen (types 1 and 4) and laminin, but had no effect on HUVE adhesion to fibronectin, confirming that VLA-2 is a collagen and laminin receptor for HUVE.

Antibodies, Monoclonal↗
PubMed2006

Up-regulated transforming growth factor beta-inducible gene h3 in rheumatoid arthritis mediates adhesion and migration of synoviocytes through alpha v beta3 integrin: Regulation by cytokines.

OBJECTIVE: To delineate the expression of transforming growth factor beta-inducible gene h3 (betaIG-H3) in rheumatoid synovitis and to determine the regulatory role of betaIG-H3 in the adhesion and migration of fibroblast-like synoviocytes (FLS). METHODS: Synovial tissue was obtained from patients with rheumatoid arthritis (RA) during joint replacement surgery, and FLS were isolated using enzymatic treatment. Immunohistochemical staining was performed to show the expression of betaIG-H3 within rheumatoid synovium. Synthesis of betaIG-H3 from FLS was determined by semiquantitative reverse transcription-polymerase chain reaction, Western blot analysis, and enzyme-linked immunosorbent assay. Cell adhesion and migration assays were performed using the YH18 peptide in the fourth fas-1 domain of betaIG-H3 and function-blocking antibodies to integrins. RESULTS: Expression of betaIG-H3 was up-regulated in RA synovial tissue compared with synovial tissue from patients with osteoarthritis. FLS isolated from RA synovial tissue constitutively produced betaIG-H3, which was up-regulated by transforming growth factor beta1, interleukin-1beta, and tumor necrosis factor alpha. Although FLS expressed a variety of integrins, betaIG-H3 mediated adhesion and migration of FLS through interaction with alpha v beta3 integrin. Cytokines failed to affect the betaIG-H3-mediated adhesion. However, migration of FLS guided by betaIG-H3 was enhanced by interferon-gamma and platelet-derived growth factor type BB. The YH18 peptide in the fourth fas-1 domain of betaIG-H3 inhibited adhesion and migration in a dose-dependent manner. CONCLUSION: The results suggest that betaIG-H3, which is abundantly expressed in RA synovial tissue, plays a regulatory role in chronic destructive inflammation through the modulation of the adhesion and migration of FLS. This finding indicates the relevance of betaIG-H3 and alpha v beta3 integrin-interacting motifs as potential therapeutic targets in this disease.

Arthritis, Rheumatoid↗
PubMed1983

Myosin isoenzymes in fast-twitch and slow-twitch muscles of normal and dystrophic mice.

An analysis of the native myosin isoenzyme composition, myosin light-chain distribution and histochemical profile of fast-twitch and slow-twitch muscles of normal and dystrophic (129 REJ dy/dy) mice has been performed, and the results correlated with the known contractile abnormalities of murine dystrophic muscles. Normal mouse slow-twitch soleus contained two isomyosins (slow myosin, SM and intermediate myosin, IM) which were electrophoretically distinct from the three major isomyosins (FM1, FM2, FM3) of fast-twitch extensor digitorum longus (e.d.l.) muscle. The calcium-activated ATPase activities of FM1, FM2, FM3 and IM at pH 9.2 were each much higher than that of SM, and this difference is reflected in the histochemical profile of muscle, as demonstrated with the myofibrillar ATPase reaction at alkaline pH. E.d.l. Type II fibres retained myofibrillar ATPase activity following pre-incubation of histochemical sections at pH 4.6, and were therefore classified Type IIB, whereas soleus Type II fibres did not, and were classified Type IIA. It was concluded that Type I (slow) fibres contain SM, Type IIA (intermediate) fibres contain IM, and Type IIB (fast) fibres contain FM1-FM3. Each electrophoretically distinct myosin contained a different combination of the five skeletal myosin light chains (LCs). Thus different normal muscles, which differed in their isomyosin profiles, differed also in their light-chain composition. Analysis of the distribution of native myosins (FM1, FM2, FM3, IM, SM, in order of decreasing gel migration rate) in dystrophic muscles revealed increased proportions of the slower-migrating forms, when compared with the distribution in the corresponding normal muscles. The shift in isomyosin distribution would explain the known decrease in the proportion of myosin light chain (LCf3) in murine dystrophic muscle. The abnormal isomyosin distribution in the dystrophic muscle is correlated with its altered histochemical characteristics, and with well-established abnormalities in its isometric and isotonic properties. It is concluded that the altered isomyosin distribution in murine dystrophic muscle would result in decreased power output per unit muscle mass when compared with normal muscle. The possibility is considered that defective myelination of the innervating nerve may contribute to these abnormalities by preventing higher frequency impulses from reaching muscle.

Animals↗