Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “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 1,243 records · Page 69Linked to original sources

Aerial migration of the Dictyostelium slug.

The Dictyostelium slug lays down curved marks in its slime sheath trail as it migrates across an agar substrate. These 'footprints' are caused by elevation of the slug anterior as it initiates a period of aerial migration and can be used as a measure of the slug's propensity for this behavior. A variety of factors have been found to affect the number of footprints created per distance migrated. Smaller slugs produce a higher incidence of footprints than larger slugs. Migration in the light and lower temperatures during migration increase footprint incidence. Activated charcoal reduces, while exogenous addition of ammonia increases, the incidence of footprints. Simulation of the three-dimensional (3D) environment of the soil suggests that aerial migration plays a role in the slug's movement through the cavities of its natural environment. A model proposes that aerial migration is initiated by a small group of continually changing prestalk cells that acts as a pacemaker and is moved around the circumference of the slug tip by the rotation of the prestalk cells. As this pacemaker reaches the upper surface of the slug it can initiate aerial migration.

Agar↗

Migration of cells from primary transplants of allo- and xenografted foetal striatal tissue in the adult rat brain.

Primary neural cells derived from human xenografts migrate extensively following transplantation into the adult rat CNS. However, it is unknown whether cells from allografts have the same capability to migrate within the adult rat brain. Moreover, it is unclear whether human-derived cells migrate to this extent as an inherent property of being in a xenograft environment, or whether it is due to the large size of the developed human brain compared with the adult rat brain. In order to address these issues we have designed an experimental paradigm to investigate the potential for cells derived from grafts of primary rat, mouse and human foetal striatal tissue to migrate following intrastriatal transplantation in an adult rat model of Huntington's disease (HD). Green fluorescent protein (GFP)-expressing rat and mouse donors and an antibody specific to human nuclear antigen enabled identification of graft-derived cells within the host brain, and double-labelling with GFP and neuronal nuclear antigen or immunostaining with human-specific tau identified graft-derived neurons. Twelve weeks post-transplantation, cells had migrated throughout the host in all groups; however, human cells and neurons had migrated significantly more than rat or mouse cells. These results demonstrate that neural cells derived from allografts are capable of migrating in the adult rat CNS and that the extent of migration is most likely determined by the size of the mature donor adult brain. This has important implications for the use of allo- and xenogeneic tissue as a source for transplantation in treating diffuse neurodegenerative disorders such as HD.

Animals↗

Antagonistic effects of seed dispersal and herbivory on plant migration.

The two factors that determine plant migration rates - seed dispersal and population growth - are generally treated independently, despite the fact that many animals simultaneously enhance plant migration rate via seed dispersal, and decrease it via negative effects of herbivory on population growth. Using extensive empirical data, we modelled the antagonistic effects of seed dispersal and herbivory by white-tailed deer on potential migration rates of Trillium grandiflorum, a forest herb in eastern North America. This novel antagonistic interaction is illustrated by maximum migration rates occurring at intermediate, but low herbivory (< 15%). Assuming herbivory < 20% and favourable conditions for population growth during post-glacial migration, seed dispersal by deer can explain rates of migration achieved in the past, in contrast to previous models of forest herb migration. However, relatively unfavourable conditions for population growth and increasingly intense herbivory by deer may compromise plant migration in the face of present and future climate change.

Animals↗

Enhancement of cell migration by corticotropin-releasing hormone through ERK1/2 pathway in murine melanoma cell line, B16F10.

Melanoma is a malignant skin cancer that displays a high rate of tumor cell migration and metastasis. This study examined how corticotropin-releasing hormone (CRH) affects the migration of melanoma cells in order to further understand the relationship between stress and tumor cell migration. The migration assay data showed that CRH treatment increased the level of B16F10 cell migration in a dose- and time-dependent manner. To determine whether the extracellular signal-regulated protein kinase 1/2 (ERK1/2) signaling pathway is involved in the upregulation of melanoma migration, cells were pretreated with an inhibitor of ERK1/2 (PD098059). The pretreatment of PD098059 blocked the increase in cell migration. Furthermore, CRH induced the phosphorylation of ERK1/2. The maximum activation of ERK1/2 by CRH was observed at 15 min. Taken together, these results suggest that CRH is an important mediator that regulates the migration of melanoma cells in the skin during stress through the ERK1/2 signaling pathway.

Animals↗

Inhibitory interactions in the patterning of trunk neural crest migration.

In avian embryos, trunk neural crest migrate segmentally through the somites, entering the rostral but not caudal somitic sclerotome. Inhibitory molecules in the caudal somite could prohibit entry of neural crest caudally, and thus restrict cell migration to rostral somite territories. Two sets of cues, peanut agglutinin (PNA) binding glycoproteins and members of the Eph family of receptor tyrosine kinases (RTKs) and their ligands appear to play this role in segmenting cell migration. Addition of exogenous PNA to neural crest migrating in trunk explants disrupts the normal segmental pattern of migration; neural crest travel in rostral and caudal regions of the somites. Members of the Eph family display the correct spatiotemporal localization to influence neural crest migration; the RTK EphB3 is expressed by neural crest, whereas the transmembrane ligand ephrin-B1 is expressed by caudal sclerotomal cells. Exogenous ephrin-B1 added to neural crest migrating in trunk explants also specifically disrupts the segmental organization of neural crest migration. Isolated neural crest avoid lanes containing ephrin-B1 in vitro; this avoidance is abolished by addition of soluble ligand. Time-lapse imaging reveals that neural crest exhibit a typical collapse response followed by process retraction upon encountering ligand. The results of these studies implicate PNA-binding glycoproteins and Eph family members in sculpting the migratory patterns of neural precursors in the peripheral nervous system.

Animals↗

Src and Cas are essentially but differentially involved in angiotensin II-stimulated migration of vascular smooth muscle cells via extracellular signal-regulated kinase 1/2 and c-Jun NH2-terminal kinase activation.

Angiotensin II (Ang II) plays an important role in several cardiovascular diseases associated with vascular smooth muscle cell (VSMC) growth and migration. Src activity is known to be required for the migration of a number of cell types. p130Cas was reported to be essential for cell migration and actin filament reorganization. Mitogen-activated protein (MAP) kinases were also reported to be critical regulatory factors for growth and migration of VSMC. However, precise intracellular mechanisms involving c-Src, p130Cas, and MAP kinases in Ang II-stimulated migration of VSMC have not been well elucidated. Here we demonstrated that Ang II rapidly and significantly stimulated tyrosine phosphorylation of Src and Cas and their association in rat aortic smooth muscle cells (RASMC). Ang II-stimulated tyrosine phosphorylation of Src and Cas and activation of ERK1/2 and JNK, but not p38, were potently inhibited by Src family tyrosine kinase inhibitors, herbimycin A (HA) and PP2. Ang II-stimulated Src and Cas association, tyrosine phosphorylation of Cas, and activation of ERK1/2 and JNK were suppressed in kinase-inactive Src (KI Src)-overexpressed RASMC. Ang II-stimulated JNK activation but not ERK1/2 activation was blocked in substrate domain-deleted Cas (DeltaSD Cas)-overexpressed RASMC. In addition, HA, PP2, ERK1/2 inhibitor, 2'-amino-3'-methoxyflavone (PD98059) and JNK inhibitor, and anthra[1,9-cd]pyrazol-6(2H)-one (SP600125) significantly inhibited Ang II-stimulated migration of RASMC. Ang II-induced colocalization of Src and Cas and migration were inhibited in both KI Src- and DeltaSD Cas-overexpressed RASMC. These findings suggest that Src and Cas are essentially but differentially involved in Ang II-stimulated migration of VSMC through the activation of ERK1/2 and JNK.

Angiotensin II↗

Human monocyte chemotaxis: migrating cells are a subpopulation with multiple chemotaxin specificities on each cell.

Only 20 to 40% of human blood monocytes were capable of responding to chemotaxins in vitro. This limit is not due to restrictions of the in vitro system, but is due to the existence of a migrating subpopulation. Over a wide range, the number of cells migrating toward a given concentration of chemotaxin was directly proportional to the number added to the chemotaxis chamber. These monocytes responded to all of the three stimuli used: human serum-derived C5a, human lymphocyte-derived chemotactic factor, and a synthetic peptide. It was possible to deactivate cells to one attractant, leaving the response to other attractants intact. This suggested that these attractants were recognized by different receptors. Several lines of evidence showed that most migrating cells had receptors for all three chemotaxins tested. Thus, if cells were assayed for migration to one attractant, no additional migration occurred when the remaining cells were assayed for migration to a different attractant. Furthermore, the same cells that had migrated toward one attractant were able to respond to other chemotaxins. We also found that a single attractant attracted as many cells as a combination of two or three attractants. Calculations from these data showed that at least 75% of the migrating monocytes have different receptors for all three attractants.

Cell Movement↗

Escherichia coli induces transuroepithelial neutrophil migration by an intercellular adhesion molecule-1-dependent mechanism.

During bacterial infections at mucosal sites, neutrophils migrate to the mucosa and cross the epithelial barrier. We have examined neutrophil migration across Escherichia coli-stimulated uroepithelial cell layers in an attempt to more fully understand this process. Stimulation of uroepithelial cells with E. coli or interleukin-1 alpha (IL-1 alpha) induced transepithelial neutrophil migration in a time- and stimulant dose-dependent manner. Uroepithelial cell lines and nontransformed uroepithelial cells expressed intercellular adhesion molecule-1 (ICAM-1) but not ICAM-2, E-selectin, or P-selectin. Epithelial ICAM-1 expression was enhanced after stimulation with E. coli or IL-1 alpha. Anti-ICAM-1 antibody reduced transepithelial neutrophil migration by 61 to 85%, indicating that neutrophils bound ICAM-1 on the epithelial surface. Antibodies to CD18 and CD11b reduced migration by 70 to 79%, suggesting that CD11b/CD18 (Mac-1) was acting as the neutrophil receptor for ICAM-1 in this process. Anti-CD11a antibodies had no effect on neutrophil migration. In conclusion, E. coli induced ICAM-1- and Mac-1-dependent transepithelial neutrophil migration. Previous studies have shown that urinary tract epithelial cells secrete IL-8 when exposed to E. coli or IL-1 alpha. These observations suggest that epithelial cells play an active role in neutrophil migration during urinary tract infections.

CD18 Antigens↗

A histone octamer blocks branch migration of a Holliday junction.

The Holliday junction is a key intermediate in genetic recombination. Here, we examine the effect of a nucleosome core on movement of the Holliday junction in vitro by spontaneous branch migration. Histone octamers consisting of H2A, H2B, H3, and H4 are reconstituted onto DNA duplexes containing an artificial nucleosome-positioning sequence consisting of a tandem array of an alternating AT-GC sequence motif. Characterization of the reconstituted branch migration substrates by micrococcal nuclease mapping and exonuclease III and hydroxyl radical footprinting reveal that 70% of the reconstituted octamers are positioned near the center of the substrate and the remaining 30% are located at the distal end, although in both cases some translational degeneracy is observed. Branch migration assays with the octamer-containing substrates reveal that the Holliday junction cannot migrate spontaneously through DNA organized into a nucleosomal core unless DNA-histone interactions are completely disrupted. Similar results are obtained with branch migration substrates containing an octamer positioned on a naturally occurring sequence derived from the yeast GLN3 locus. Digestion of Holliday junctions with T7 endonuclease I establishes that the junction is not trapped by the octamer but can branch migrate in regions free of histone octamers. Our findings suggest that migration of Holliday junctions during recombination and the recombinational repair of DNA damage requires proteins not only to accelerate the intrinsic rate of branch migration but also to facilitate the passage of the Holliday junction through a nucleosome.

Animals↗

Novel p27(kip1) C-terminal scatter domain mediates Rac-dependent cell migration independent of cell cycle arrest functions.

Hepatocyte growth factor (HGF) signaling via its receptor, the proto-oncogene Met, alters cell proliferation and motility and has been associated with tumor metastasis. HGF treatment of HepG2 human hepatocellular carcinoma cells induces cell migration concomitant with increased levels of the p27(kip1) cyclin-cdk inhibitor. HGF signaling resulted in nuclear export of endogenous p27 to the cytoplasm, via Ser-10 phosphorylation, where it colocalized with F-actin. Introduction of transducible p27 protein (TATp27) was sufficient for actin cytoskeletal rearrangement and migration of HepG2 cells. TATp27 mutational analysis identified a novel p27 C-terminal domain required for cell migration, distinct from the N-terminal cyclin-cyclin-dependent kinase (cdk) binding domain. Loss or disruption of the p27 C-terminal domain abolished both actin rearrangement and cell migration. The cell-scattering activity of p27 occurred independently of its cell cycle arrest functions and required cytoplasmic localization of p27 via Ser-10 phosphorylation. Furthermore, Rac GTPase was necessary for p27-dependent migration but alone was insufficient for HepG2 cell migration. These results predicted a migration defect in p27-deficient cells. Indeed, p27-deficient primary fibroblasts failed to migrate, and reconstitution with TATp27 rescued the motility defect. These observations define a novel role for p27 in cell motility that is independent of its function in cell cycle inhibition.

Actins↗

Lipopolysaccharide/interferon-gamma and not transforming growth factor beta inhibits retinal microglial migration from retinal explant.

BACKGROUND: /aims: The retina possesses a rich network of CD45(+) positive myeloid derived cells that both surround inner retinal vessels and lie within the retina (microglia). Microglia migrate and accumulate in response to neurodegeneration and inflammation. Although microglia express MHC class II, their role remains undefined. The aims of this study are to investigate changes in human microglia phenotype, migration, and activation status in response to pro-inflammatory and anti-inflammatory stimulation. METHODS: Donor eyes were obtained from the Bristol Eye Bank with consent and whole retina was removed. 5 mm retinal trephines were cultured in glucose enhanced RPMI on cell culture insert membranes for up to 72 hours. The effects of lipopolysaccharide/interferon-gamma (LPS/IFNgamma) and transforming growth factor beta inhibits (TGFbeta) stimulation, alone or in combination, on migration, phenotype, and activation status (iNOS expression) of microglia were studied using immunofluorescence and cytokine analysis by ELISA. RESULTS: CD45(+) MHC class II(+) retinal microglia were observed within retinal explants, and in culture microglia readily migrated, adhered to culture membrane, downregulated MHC class II expression, and produced interleukin 12 (IL-12) and tumour necrosis factor alpha (TNFalpha). Following LPS/IFNgamma stimulation microglia remained MHC class II(-) iNOS(-), and secreted IL-10. Migration was suppressed and this could be reversed by neutralising IL-10 activity. TGFbeta did not affect ability of microglia to migrate and was unable to reverse LPS/IFNgamma induced suppression. CONCLUSIONS: Microglia readily migrate from retinal explants and are subsequently MHC class II(-), iNOS(-), and generate IL-12. In response to LPS/IFNgamma microglia produce IL-10, which inhibits both their migration and activation. TGFbeta was unable to counter LPS/IFNgamma effects. The data infer that microglia respond coordinately, dependent upon initial cytokine stimulation, but paradoxically respond to classic myeloid activation signals.

Cell Adhesion↗

Migration-associated volume changes in neutrophils facilitate the migratory process in vitro.

Neutrophil granulocytes, while migrating, undergo substantial shape changes from the round, resting state to a polarized phenotype. In the present study, we monitored cell volume changes in neutrophils migrating toward the chemotactic agent N-formyl-methionyl-leucyl-phenylalanine (FMLP) in collagen gels. Neutrophil volume was measured through optical sectioning on a confocal microscope and three-dimensional reconstruction. This method correlated well with Coulter counter volume measurements. Migrating neutrophils displayed a significant volume increase of 35-60%. The cell swelling appeared to depend on sodium/proton antiport activity because it was abrogated by amiloride and dimethyl-amiloride, inhibitors of the antiport, and by substitution of sodium in the buffers by choline, which is not transported by the antiport. Neutrophils exposed to FMLP gradients through impenetrable filters also displayed significant volume changes, whereas cells placed on similar filters in homogeneous concentrations of FMLP did not. This supports the notion of a differential volume response depending on the mode of presentation of the chemotactic agent. The role of volume increase in facilitating neutrophil migration was adduced by two lines of evidence: 1) hyposmolar swelling enhanced and hyperosmolar shrinking decreased neutrophil migration toward FMLP in Boyden chambers and 2) sodium/proton antiport inhibitors decreased neutrophil migration; however, this was reversed in hyposmolar buffers, which induced a volume increase similar to that seen in normal migrating cells. The migration-associated volume increase may be a crucial event for the ability of neutrophils to function as the first line of defense at sites of infection.

Amiloride↗

Intestinal epithelial cytoskeleton selectively constrains lumen-to-tissue migration of neutrophils.

Migration of neutrophils (polymorphonuclear leukocytes; PMN) across polarized epithelia is asymmetrical: basolateral-to-apical (physiologically directed) migration is far more efficient than migration in the reverse direction, suggesting the presence of luminal retention signal(s). Following pilot observations, we used polarized intestinal epithelial monolayers (T84) to examine whether asymmetrical constraint of migration afforded by the epithelial cytoskeleton might underlie such retention signals. Rearrangement of epithelial cortical F-actin accompanied PMN transepithelial migration (in either direction) and was prevented by preloading monolayers with the F-actin stabilizing agent phallacidin. Although phallacidin preloading did not influence physiologically directed PMN transepithelial migration, such treatment greatly enhanced migration in the reverse direction (i.e., effective loss of luminal retention signal). 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) preloading also prevented epithelial cortical actin rearrangements and selectively resulted in loss of luminal retention signal(s). BAPTA preloading did not influence resistance or forskolin-induced Cl- secretion, and phallacidin preloading did not influence resistance or carbachol-induced Cl- secretion, suggesting that barrier function and surface polarity were maintained under these conditions. These and supplementary data suggest that epithelial actin (but not microtubule) cytoskeletal reordering asymmetrically influences PMN migration and underlies, at least in part, the observed signal that biases for retention of PMN in the luminal space.

Actins↗

Role of K(+) channel expression in polyamine-dependent intestinal epithelial cell migration.

Polyamines are essential for cell migration during early mucosal restitution after wounding in the gastrointestinal tract. Activity of voltage-gated K(+) channels (Kv) controls membrane potential (E(m)) that regulates cytoplasmic free Ca(2+) concentration ([Ca(2+)](cyt)) by governing the driving force for Ca(2+) influx. This study determined whether polyamines are required for the stimulation of cell migration by altering K(+) channel gene expression, E(m), and [Ca(2+)](cyt) in intestinal epithelial cells (IEC-6). The specific inhibitor of polyamine synthesis, alpha-difluoromethylornithine (DFMO, 5 mM), depleted cellular polyamines (putrescine, spermidine, and spermine), selectively inhibited Kv1.1 channel (a delayed-rectifier Kv channel) expression, and resulted in membrane depolarization. Because IEC-6 cells did not express voltage-gated Ca(2+) channels, the depolarized E(m) in DFMO-treated cells decreased [Ca(2+)](cyt) as a result of reduced driving force for Ca(2+) influx through capacitative Ca(2+) entry. Migration was reduced by 80% in the polyamine-deficient cells. Exogenous spermidine not only reversed the effects of DFMO on Kv1.1 channel expression, E(m), and [Ca(2+)](cyt) but also restored cell migration to normal. Removal of extracellular Ca(2+) or blockade of Kv channels (by 4-aminopyridine, 1-5 mM) significantly inhibited normal cell migration and prevented the restoration of cell migration by exogenous spermidine in polyamine-deficient cells. These results suggest that polyamine-dependent intestinal epithelial cell migration may be due partially to an increase of Kv1.1 channel expression. The subsequent membrane hyperpolarization raises [Ca(2+)](cyt) by increasing the driving force (the electrochemical gradient) for Ca(2+) influx and thus stimulates cell migration.

Animals↗

Polyamines are necessary for cell migration by a small intestinal crypt cell line.

Studies from our laboratory have shown that polyamines are essential for the normal repair of duodenal erosions induced in vivo in a rat stress-ulcer model. In that model, the inhibition of ornithine decarboxylase, a rate-limiting enzyme of polyamine biosynthesis, with alpha-difluoromethylornithine (DFMO) almost entirely prevented healing. Healing could be restored by oral polyamines. In this paper, we have investigated whether the polyamines are required for the early stages of epithelial restitution using an IEC-6 cell culture model of cell migration. Treatment of the cells with DFMO for 4 days reduced cell migration 80%. Migration could be restored to normal by concomitant treatment with putrescine (PUT), spermidine (SPD), or spermine (SPM), but not by their addition during the migration period (6 h) only. If DFMO treatment was not begun until the migration period, it still reduced cell migration 20%, and this deficit could not be restored by concomitant addition of the polyamines. Intracellular polyamine levels at these times, i.e., 6 h or 4 days, were an important factor in these results. Only PUT was undetectable after 6 h of DFMO. SPD and SPM were still at normal levels at 6 h. SPD was undetectable at 4 days, but SPM was still at 40% of normal. These data give added importance to PUT because its absence reduced cell migration after only 6 h, while SPD and SPM were still present in normal amounts. Perhaps exogenous SPD and SPM restored cell migration when present with DFMO for 4 days treatment primarily because they contributed to intracellular PUT through the acetyltransferases.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Phospholipase A2 stimulation of rat intestinal epithelial cell (IEC-6) migration.

The effect of phospholipase A2 (PLA2) on intestinal epithelial cell migration was investigated using an in vitro wounding model of confluent monolayers of IEC-6. PLA2 (0.001-2 U/ml) enhanced IEC-6 cell migration in a dose dependent manner. Addition of 4-bromophenacyl bromide (BPB) (a PLA2 inhibitor) to PLA2 completely blocked the migration-promoting effect. However, addition of piroxicam (a cyclooxygenase inhibitor) or nordihydroguaiaretic acid (a lipoxygenase inhibitor) had no influence on the effect. Lysophosphatidylcholine (lysoPC) (0.01-5,000 ng/ml), one of the products of phosphatidylcholine by PLA2, dose-dependently enhanced IEC-6 cell migration as well. A combination of PsLA2 (1 U/ml) and lysoPC (1,000 ng/ml) had no additive effect or migration. Moreover, the migration-promoting effect of PLA2 that was blocked by BPB was recovered by lysoPC. After pretreatment of IEC-6 cells with replication-inhibiting doses of mitomycin C, the enhanced migration induced by PLA2 or lysoPC was still observed. These observations suggest that PLA2 may, independently of proliferation, enhance intestinal epithelial cell migration mainly via lysoPC.

Acetophenones↗

Migration of intestinal intraepithelial lymphocytes into a polarized epithelial monolayer.

Intraepithelial lymphocytes (IEL) are a phenotypically distinct population of lymphocytes that reside in mucosal epithelia, below the intercellular tight junctions. Although adhesive functions of this population have been previously studied, relatively little is known about IEL migration from the microvasculature into the epithelium. We demonstrated that cultured human IEL were capable of migration into polarized epithelial cells in vitro, where they assumed a subjunctional position, identical to that observed in vivo. The migration was rapid and efficient and was directionally polarized, such that IEL migrated into epithelial monolayers from the basolateral, but not the apical, aspect. After a 4-h period of residence, up to one-half of the IEL then exited the monolayer basolaterally. Migration was partially inhibited by pertussis toxin, suggesting a potential mechanism for IEL migration by chemokine receptor-mediated signaling. The conditions and ligand pairs used in IEL migration were different from those for neutrophils, another cell type known to migrate through epithelia. This system may serve as a model for microenvironmental homing of IEL into the epithelium.

CD8-Positive T-Lymphocytes↗

Shear stress inhibits smooth muscle cell migration via nitric oxide-mediated downregulation of matrix metalloproteinase-2 activity.

Vascular smooth muscle cell (SMC) migration is a hallmark of intimal hyperplasia (IH), the progression of which is affected by hemodynamic conditions at the diseased site. The realization that SMCs are exposed to blood flow in both denuded vessels (direct blood flow) and intact vessels (interstitial blood flow) motivated this study of the effects of fluid flow shear stress (SS) on SMC migration. Rat aortic SMCs were seeded onto Matrigel-coated cell culture inserts, and their migratory activity toward PDGF-BB when exposed to SS in a rotating disk apparatus was quantified. Four hours of either 10 or 20 dyn/cm2 SS significantly inhibited SMC migration to the bottom side of the insert. This inhibition was associated with downregulation of SMC matrix metalloproteinase (MMP)-2 activation. Four hours of 10 dyn/cm2 SS also drastically increased SMC production of NO. A NO synthase inhibitor (N(G)-nitro-L-arginine methyl ester; 100 microM) abolished the shear-induced increase in SMC NO production as well as the inhibition of migration and MMP-2 activity. A NO donor (S-nitroso-N-acetyl-penicillamine; 500 microM) suppressed SMC migration via the reduction of both total and active MMP-2 levels. Addition of 10 microM MMP-2 inhibitor I to inserts significantly reduced SMC migration. Western blots showed no effect of 4 h of 20 dyn/cm2 SS on SMC production of PDGF-AA, another chemical known to suppress SMC migration. Thus it appears that SS acts to suppress SMC migration by upregulating the cellular production of NO, which in turn inhibits MMP-2 activity.

Animals↗