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 1,333 records · Page 74Linked to original sources
PubMed2005

EBRA-FCA for measurement of migration of the femoral component in surface arthroplasty of the hip.

Studies on the migration of an implant may be the only way of monitoring the early performance of metal-on-metal prostheses. The Ein Bild Roentgen Analyse--femoral component analysis (EBRA-FCA) method was adapted to measure migration of the femoral component in a metal-on-metal surface arthroplasty of the hip using standard antero-posterior radiographs. In order to determine the accuracy and precision of this method a prosthesis was implanted into cadaver bones. Eleven series of radiographs were used to perform a zero-migration study. After adjustment of the femoral component to simulate migration of 3 mm the radiographs were repeated. All were measured independently by three different observers. The accuracy of the method was found to be +/- 1.6 mm for the x-direction and +/- 2 mm for the y-direction (95% percentile). The method was validated using 28 hips with a minimum follow-up of 3.5 years after arthroplasty. Seventeen were sound, but 11 had failed because of loosening of the femoral component. The normal (control) group had a different pattern of migration compared with that of the loose group. At 29.2 months, the control group showed a mean migration of 1.62 mm and 1.05 mm compared with 4.39 mm and 4.05 mm in the failed group, for the centre of the head and the tip of the stem, respectively (p = 0.001). In the failed group, the mean time to migration greater than 2 mm was earlier than the onset of clinical symptoms or radiological evidence of failure, 19.1 versus 32.2 months (p = 0.001) and 24.8 months (p = 0.012), respectively. EBRA-FCA is a reliable and valid tool for measuring migration of the femoral component after surface arthroplasty and can be used to predict early failure of the implant. It may be of value in determining the long-term performance of surface arthroplasty.

Adult↗
PubMed2000

Are hyaluronan receptors involved in three-dimensional cell migration?

Hyaluronan (HA), an unbranched polysaccharide consisting of repeated glucuronic acid/N-acetylglucosamine disaccharide units, is ubiquitously present in the extracellular matrix of many tissues (for a more comprehensive review see: Fraser et al., 1997). Increased amounts of hyaluronan are produced by solid tumors and tumor-associated fibroblasts, and tumor-induced HA is correlated with poor prognosis. HA is well known to stimulate the migration of a large variety of cell types. Stimulation of cell migration by HA has been explained by different mechanisms. HA was shown to specifically bind to cell surface receptors, and inhibition of HA-receptor function was demonstrated to decrease cell migration and tumor growth. On the other hand, HA as a large hydrophilic molecule is also known to modulate the extracellular packing of collagen and fibrin, leading to increased fiber size and porosity of extracellular substrates. Hence a modified matrix architecture might similarly account for increased locomotion of cells. In this review, we attempted to summarize the available data on HA-induced cell migration, with particular emphasis on the role of HA receptors in three-dimensional cell migration. Although the HA receptor CD44 has been shown to mediate migration of cells over two-dimensional hyaluronan-coated surfaces in vitro, there is only little evidence that HA-binding to CD44 or other HA receptors has major impact on the locomotion of cells through three-dimensional matrices in vivo. We showed recently that the promigratory effect of HA in fibrin gels is largely due to HA-mediated modulation of fibrin polymerization. By increasing the porosity of fibrin gels, HA strongly accelerates cell migration. The porosity of matrices therefore appears as an important and probably underestimated determinant of cell migration and tumor spread.

Animals↗
PubMed2004

Immunoblockage of 9-O-acetyl GD3 ganglioside arrests the in vivo migration of cerebellar granule neurons.

During development of the cerebellum, radial glial cells guide the migration of granule cell precursors from the external granular cell layer toward the internal granular cell layer. The cellular membranes of migrating neurons and glial fibers organize a specialized migration junction at the site of contact between these cells, and several molecules have been implicated in the control of this glial-guided neuronal migration program. The monoclonal antibody Jones (mAb Jones) recognizes the ganglioside 9-O-acetyl GD3, which is expressed in migratory profiles in the developing and adult CNS. Recently, this ganglioside was suggested to play a role in neuronal migration in cerebellar cultures. In this report, we use antibody perturbation assays to investigate a possible role of 9-O-acetyl GD3 in the neuronal migration program in vivo. The results show that chronic intracerebroventricular administration of mAb Jones arrests neuronal migration in the developing cerebellum of live animals. Proliferating granule cell precursors were labeled with 5-bromo-2'-deoxyuridine (BrdU), and their migratory behavior was analyzed and compared with control groups. Immunoblockage of 9-O-acetyl GD3 arrests 43% of the BrdU-labeled granule precursors in the external granular cell layer. Together with our previous results, this report strongly suggests that the ganglioside 9-O-acetyl GD3 plays a crucial role in the migration of cerebellar granule cells along radial glial fibers in the developing rat cerebellum.

Animals↗
PubMed2006

Matrix metalloproteinase 2 (MMP2) and MMP9 secreted by erythropoietin-activated endothelial cells promote neural progenitor cell migration.

We investigated the hypothesis that endothelial cells activated by erythropoietin (EPO) promote the migration of neuroblasts. This hypothesis is based on observations in vivo that treatment of focal cerebral ischemia with EPO enhances the migration of neuroblasts to the ischemic boundary, a site containing activated endothelial cells and angiogenic microvasculature. To model the microenvironment within the ischemic boundary zone, we used a coculture system of mouse brain endothelial cells (MBECs) and neural progenitor cells derived from the subventricular zone of the adult mouse. Treatment of MBECs with recombinant human EPO (rhEPO) significantly increased secretion of matrix metalloproteinase 2 (MMP2) and MMP9. rhEPO-treated MBEC supernatant as conditioned medium significantly increased the migration of neural progenitor cells. Application of an MMP inhibitor abolished the supernatant-enhanced migration. Incubation of neurospheres alone with rhEPO failed to increase progenitor cell migration. rhEPO activated phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and extracellular signal-regulated kinase (ERK1/2) in MBECs. Selective inhibition of the PI3K/Akt and ERK1/2 pathways significantly attenuated the rhEPO-induced MMP2 and MMP9, which suppressed neural progenitor cell migration promoted by the rhEPO-activated MBECs. Collectively, our data show that rhEPO-activated endothelial cells enhance neural progenitor cell migration by secreting MMP2 and MMP9 via the PI3K/Akt and ERK1/2 signaling pathways. These data demonstrate that activated endothelial cells can promote neural progenitor cell migration, and provide insight into the molecular mechanisms underlying the attraction of newly generated neurons to injured areas in brain.

Animals↗
PubMed1986

Control of binucleate cell migration in the placenta of sheep and goats.

In the ruminant placenta 15-20% of the trophectodermal epithelium consists of granulated binucleate cells (BNC). In the sheep the granules contain ovine placental lactogen (oPL). These cells migrate from the trophectoderm to form fetomaternal hybrid tissue from implantation to term. The number of BNC, their percentage migration and the potential secretory activity of the syncytium they form were estimated by semiquantitative transmission electron-microscopical techniques after several surgical techniques and hormone or drug infusions. BNC numbers decrease normally just before parturition, and this fall could be eliminated by fetal hypophysectomy or induced early by administration of tetracosactrin to intact or hypophysectomized fetuses. If only one twin was treated with tetracosactrin the placenta of the untreated twin did not show the fall in BNC numbers found in the other unless it died in utero some time before sampling. This indicates fetal control of BNC number and migration. However, fetal catheterization, hypophysectomy, stalk section, adrenalectomy, infusion of mouse epidermal growth factor or bromocriptine had little or no effect on binucleate cell numbers or migration percentages. Maternal carunclectomy, ovariectomy, or epostane or bromocriptine administration also had no consistent significant effect. Previous reports of degeneration of BNC structure plus a decrease in their number (with bromocriptine) or an increase in migration frequency (after adrenalectomy or stalk section) have not been confirmed by this study. The BNC migration delivers the oPL-containing BNC granules close to the maternal circulation but the variation in migration seems only loosely correlated with the reported maternal oPL concentrations. The results indicate that BNC migration is independent of the hormonal milieu, but that BNC production is greatly modified by the hormonal changes just before parturition, with cortisol production by the fetus a possible primary cause.

Adrenalectomy↗
PubMed2005

Convergence to the island-model coalescent process in populations with restricted migration.

In this article we apply some graph-theoretic results to the study of coalescence in a structured population with migration. The graph is the pattern of migration among subpopulations, or demes, and we use the theory of random walks on graphs to characterize the ease with which ancestral lineages can traverse the habitat in a series of migration events. We identify conditions under which the coalescent process in populations with restricted migration, such that individuals cannot traverse the habitat freely in a single migration event, nonetheless becomes identical to the coalescent process in the island migration model in the limit as the number of demes tends to infinity. Specifically, we first note that a sequence of symmetric graphs with Diaconis-Stroock constant bounded above has an unstructured Kingman-type coalescent in the limit for a sample of size two from two different demes. We then show that circular and toroidal models with long-range but restricted migration have an upper bound on this constant and so have an unstructured-migration coalescent in the limit. We investigate the rate of convergence to this limit using simulations.

Algorithms↗
PubMed1996

Migration of human gingival fibroblasts over guided tissue regeneration barrier materials.

The purpose of this investigation was to determine the ability of human gingival fibroblasts, in vitro, to migrate along a chemotactic gradient over 3 different guided tissue regeneration barrier materials; i.e., polytetrafluoroethylene, polylactic acid, and sterile calcium sulfate. Forty petri dishes were divided into 4 equal groups. In each group of 10 dishes, a different barrier material served as the fibroblast substrate with the polystyrene floor of one group of Petri dishes serving as the control. The under agarose technique of measuring cell migration was employed using platelet derived growth factor-BB homodimer as the chemoattractant and Hanks balanced salt solution to test random migration. In addition, fibroblasts were directly cultured on triplicate sets of barrier materials and the control surface for 24 hours and examined by scanning electron microscopy. Comparative analysis of the fibroblast migration data showed the mean migration distance (adjusted for random migration) for controls to be significantly greater than any of the three barrier materials. Further, mean migration distance over calcium sulfate was significantly greater when compared to that of the polylactic acid barrier group. All other comparisons between groups were not statistically significant. Scanning electron microscopic examination fibroblasts cultured directly on barrier membranes and compared to controls indicated that the calcium sulfate substrate appeared to facilitate cell attachment and spreading whereas cells on polytetrafluoroethylene and polylactic acid barriers exhibited a morphology not conducive to migration or, in many cases, cell health. Based on these limited in vitro results and, given the 3 barrier materials considered, it would appear that calcium sulfate offers the greater potential for guided tissue regeneration in surgical sites where primary wound closure cannot be obtained.

Becaplermin↗
PubMed1997

Migration of gingival fibroblasts on fibronectin and laminin.

The migrational behavior of fibroblasts is critical for the maintenance and healing of the periodontium. The purpose of this study was to determine, in vitro, the differences found in gingival fibroblast migration on the following substrates: fibronectin, laminin, bovine serum albumin (BSA), or plastic. Filter paper strips soaked in solutions of the test molecules were placed in 35 mm culture dishes. Equimolar amounts of the various proteins were allowed to dry onto the plastic in a discrete band. The bands were masked and 5.0 x 10(4) cells seeded. Rat gingival fibroblasts were allowed to attach for 1.5 hours and the protein bands uncovered and incubation continued for 24 hours under standard conditions. Cells were fixed, stained and cell images captured, computer digitized and migrational areas and cell numbers and areas quantified after converting pixels to microm. Cell migration was enhanced on fibronectin substrates. Statistically significant differences (P < 0.01) were found for total area covered (fibronectin, mean = 110.8 mm2 vs. controls: plastic, mean = 28.2 mm2; BSA, mean = 18.2 mm2) and the number of cells migrating as compared to controls (fibronectin, mean = 1184 vs. controls: plastic, mean = 304, BSA, mean = 230). No significant differences in area covered or numbers of cells migrating were found between controls and cells exposed to other substrates. Mean spread area per cell was not statistically significantly different for any of the conditions. Numbers of cells migrating on substrates other than fibronectin were reduced even more when protein synthesis was inhibited using cycloheximide. In this system fibronectin serves as a cue to recruit significantly greater numbers of fibroblasts to migrate for greater distances than the other molecules tested.

Animals↗
PubMed1998

A new design of the esophageal Wallstent endoprosthesis resistant to distal migration.

OBJECTIVE: Because plastic-covered metallic stents used in the palliation of patients with unresectable esophageal cancer are associated with significant rates of migration, particularly when the lower end of the stent projects into the gastric fundus, the purpose of this study was to establish whether two new prototype designs of the Wallstent esophageal endoprosthesis are prone to migration. SUBJECTS AND METHODS: A cylindrical stent and a conical stent were studied. Both designs included plastic covering inside the metallic mesh. In addition, the conical device incorporated a variation in the braiding angle between the upper and lower parts of the endoprosthesis. Ten conical stents and eight cylindrical stents were inserted in 18 patients with tumors involving the gastroesophageal junction who were followed up with esophagography and endoscopy. RESULTS: All insertions of stents were successful. Two cylindrical stents (25%) migrated distally. Two conical stents (20%) migrated proximally. One perforation occurred that was associated with distal migration of a cylindrical stent. CONCLUSION: The frequency of distal migration of cylindrical stents is unacceptably high. Conical stents are resistant to distal migration, although improvements in design are required to deal with the problem of proximal migration.

Adenocarcinoma↗
PubMed1992

Influence of the embryo on intrauterine migration in sheep.

Mechanisms of intrauterine migration were examined in 55 ewes. In the first experiment, corpora lutea were removed from unilaterally ovariectomized ewes on d 4 (d 0 = estrus) and pregnancy was maintained by giving exogenous progesterone. In Exp. 2, the reproductive tract was altered surgically such that embryos initially entered the uterine horn contralateral to the site of ovulation. In Exp. 3, ewes received beads of silastic polydimethylsiloxane that released either cholesterol or estradiol-17 beta in an attempt to mimic embryonic synthesis of estradiol. In the fourth experiment, unilaterally ovariectomized ewes were superovulated and spacing of embryos within the uterus was then examined. In all experiments, ewes were slaughtered on d 15 and recovery of embryos or beads from each uterine horn indicated that migration had occurred. All ewes in Exp. 1 and 2 that had two conceptuses experienced embryonic migration. Beads impregnated with estradiol migrated farther (P less than .01) than cholesterol-containing beads (27.6 +/- 4.3 vs 12.5 +/- 1.6 cm, respectively). In Exp. 4, only one conceptus had migrated into the contralateral horn in all ewes. These results demonstrated that 1) embryonic migration was not affected by local vs systemic exposure to progesterone, 2) embryos migrated into the unoccupied horn, regardless of the initial horn of entry, 3) estradiol may stimulate embryonic migration, and 4) conceptuses were not equally distributed between horns.

Animals↗
PubMed1998

Uterotrophic assay of two concentrations of migrates from each of 23 polystyrenes administered orally (by gavage) to immature female Wistar rats.

The Styrene Steering Committee (SSC) of the European Chemical Industry Council (CEFIC) sponsored this work to address any concern that styrene dimers and trimers that might migrate from polystyrene containers into food could possess some estrogenic activity and thus possibly affect human health. All phases of the study were conducted in conformance with GLP regulations and without knowledge of the oligomer migrates tested. All activities were managed and audited under a third-party contract between the SSC and Argus International. Low and high doses of the styrene oligomer migrates of 23 polystyrene samples [i.e. 9 general purpose polystyrenes (GPPS), 8 high impact polystyrenes (HIPS) and 6 expandable polystyrenes (EPS)] were tested for estrogenicity in an in vivo uterotrophic assay (immature female rat model). This model is considered to be the "gold standard" for use in screening for estrogenic effects because it evaluates both direct and indirect potential effects. The two concentrations of migrates of each of the 23 polystyrenes tested were selected to simulate daily human consumption of a low and high amount of food. Representative dimer and trimer concentrations were obtained in conformance with EEC Council Directives and calculated to be at levels simulating human consumption of 0.5 or 5 kg of food for the GPPS and the HIPS samples and of 0.5 or 3.15 kg of food for the EPS samples, respectively. The study was conducted in a series of three blocks. Each block included concurrent untreated control (negative control), vehicle control (25% ethanol, 20 ml/kg/day) and positive control (diethylstilbestrol-dipropionate, DES-DP, 5 micrograms/kg/day) groups, and low and high doses of each of 7 (1 block) or 8 (2 blocks) polystyrene oligomer migrates. Each group in each block consisted of 10 immature Wistar (Chbb: THOM-SPF) female rats. Beginning when the rats were 22 +/- 1 days of age, each rat was appropriately handled (untreated control group) or administered twice daily oral (gavage) dosages of the vehicle, positive control agent or one of the two doses of the migrates of each polystyrene for 4 consecutive days and then sacrificed at 26 +/- 1 days of age. The uterus of each rat was weighed, and the uterine weight was compared with the terminal body weight. The positive control agent (DES-DP, 5 micrograms/kg/day) significantly increased both absolute and relative (to terminal body weight) uterine weights, as compared to the untreated and vehicle control group values in each block, demonstrating sensitivity and response of the animals to an estrogenic agent. None of the 23 polystyrene oligomer migrates tested at low and high doses demonstrated biologically important or statistically significant differences from the untreated or vehicle control group values for absolute or relative (to body weight) uterine weights. Based on these data, it is concluded that low and high doses of the 23 polystyrene oligomer migrates tested did not induce an estrogenic response.

Animals↗
PubMedDate not supplied

Quantification of leukocyte migration: improvement of a method.

Eighteen different permeable membrane supports with and without confluent endothelial cell monolayers were incubated with normal donor derived neutrophils in the upper chambers of a 24 multiwell double chamber system. In order to study transmembrane or transendothelial leukocyte migration leukocytes were stimulated by chemoattractants, or endothelial cells were activated by IL-1. After coincubation the membrane supports building the upper chambers were discarded. Using this technique, leukocytes that had migrated into the lower chamber were exposed to the fluorescent dye calcein AM without additional washing or transfer steps. Absolute cell counts were determined computer assisted using dilution series of calcein AM labeled leukocytes as standards. Serial dilutions of neutrophils exposed to calcein AM showed reproducible linear fluorescence intensity, and relative fluorescence intensity correlated significant with cell counts (r2 = 0.974, p < 0.0001). Out of 18 membrane supports only one was suitable for our assay set up. Best technical and optical performance was achieved with a membrane made of polyethylene terephtalate with a pore size of 3 mm at a pore density of 0.8 x 10(6)/cm2. Stimulation of leukocytes or endothelium by FMLP or IL-1 revealed an increase of transendothelial migration to 7.2 +/- 1.8 x 10(5) PMN and 5.1 +/- 0.7 x 10(5) PMN respectively if compared with medium (0.6 +/- 0.2 x 10(5) PMN). IL-1 induced migration of neutrophils was inhibited by anti IL-1 autoantibodies derived from chronic renal failure patients (IL-1: 100% of PMN migrated, anti IL-1 antibody: 39% of PMN migrated, control antibody: 84% of PMN migrated). In summary, a simple fluorimetric assay was established for the quantification of transmembrane and transendothelial leukocyte migration.

Autoantibodies↗
PubMed1996

Transvascular and interstitial migration of neutrophils in rat mesentery.

OBJECTIVE: The consequential implications of the leukocyte-endothelial cell adhesion reaction, as well as the subsequent migratory activity of the leukocytes within the interstitium proper, are currently known only in general phenomenological terms. Our objective was to carry out a detailed quantitative analysis of transendothelial and interstitial migration. METHOD: We incorporated several new features, such as the video recording of time-lapse photography in conjunction with the time history of individual leukocytes under the influence of representative stimulators and inhibitors. The mesentery was suffused with the chemical activator N-formyl-met-leu-phe (fMLP, 5 x 10(-8) M) and histamine (10(-6) M) for periods up to 3 h. This leads to an attachment of neutrophils preferentially to the walls of small postcapillary venules followed by migration into the adjacent interstitium. RESULTS: The time interval between the initial neutrophil adhesion to the luminal side of the venules and their first appearance on the abluminal side of the venule wall was about 25 min. The time interval for the actual physical migration across the endothelium was only about 1-2 min. There was an initial increase in the number of neutrophils migrating across the wall per unit time after the application of fMLP. However, this effect then gradually decreased over the course of 1 h. In the extravascular tissue, the neutrophils appeared to migrate along random pathways with an average trajectory away from the venular wall. When histamine (1 microM) was applied topically in conjunction with fMLP, the overall migratory flux across the venular wall increased, although the cells migrated comparatively short distances into the interstitium. After pretreatment with phalloidin (25 micrograms/kg), an actin cross-linking agent, neutrophil adhesion and migration in response to fMLP stimulation was reduced. The mast cell stimulator 48/80 (25 mg/ml) resulted in rapid degranulation, which was accompanied by an insignificant increase in neutrophil diapedesis. After fMLP stimulation there was reduced neutrophil emigration in the presence of mast cell inhibitors, such as lodoxamide (1 microgram/kg) and ketotifin (microgram/kg). CONCLUSIONS: Our results demonstrate that both the endothelial cells and interstitial mast cells are involved in the rate of transvascular migration of leukocytes across postcapillary venules and into the interstitium.

Animals↗
PubMed2002

Ephrin-as cooperate with EphA4 to promote trunk neural crest migration.

Trunk neural crest cells delaminate from the dorsal neural tube and migrate on two distinct pathways: a dorsolateral route, between the ectoderm and somites,and a ventromedial route, through the somitic mesoderm. Neural crest cells that migrate ventromedially travel in a segmental manner through rostral half-somites, avoiding caudal halves. Recent studies demonstrate that various molecular cues guide the migration of neural crest cells, primarily by serving as inhibitors to premature pathway entry orby preventing neural crest from entering inappropriate territories. Trajectories of migrating trunk neural crest are well organized and generally linear in nature, suggesting that positive, migration-promoting factors may be responsible for this organized cell behavior. However, the identity of these factors and their function are not well understood. Here we examine the expression of members of the EphA subclass of receptor tyrosine kinases and ephrins using RT-PCR and immunocytochemistry. Neural crest cells express ephrins and EphA4 at distinct stages during their migration. In functional analyses, addition of ephrin-A2-, ephrin-A5-, and EphA4-Fc disrupted the segmental organization of trunk neural crest migration in explants: neural crest cells entered rostral and caudal halves of somites. Finally, to test the specific effects of these factors on cell behavior, neural crest cells were exposed in vitro to substrate-bound EphA and ephrin-As. Surprisingly, neural crest cells avoided ephrin-A2 or ephrin-A5 substrates; this avoidance was abolished by the addition of EphA4. Together, these data suggest that ephrin-As and EphA4 cooperate to positively promote the migration of neural crest cells through rostral half somites in vivo.

Animals↗
PubMed2000

A study of SPARC and vitronectin localization and expression in pediatric and adult gliomas: high SPARC secretion correlates with decreased migration on vitronectin.

SPARC is a secreted glycoprotein that interacts with extracellular matrix (ECM) proteins to promote de-adhesion of cells from the matrix, thereby inducing a biological state conducive to cell migration. We have demonstrated that SPARC is highly expressed in gliomas (grades II-IV) and promotes glioma invasion in vitro. Therefore, the protein itself or its mechanisms of action might become therapeutic targets to arrest glioma invasion. Vitronectin is an ECM protein found in the blood vessel basement membranes and may promote glioma invasion along these structures. It binds to SPARC in vitro. However, it is not known whether SPARC and vitronectin colocalize and/or interact to contribute to brain tumor cell migration in vivo. In this study, we immuno-histochemically determined if the grade I juvenile pilocytic astrocytomas (JPAs) also express SPARC, if vitronectin is expressed in grades I, II, and IV astrocytomas, and if the proteins colocalize in brain tumors in vivo. We performed western blot analyses to determine if different grades of tumors had different intracellular and/or secreted levels of SPARC and vitronectin. We performed migration assays to determine whether vitronectin is a permissive substrate for glioma migration, and whether the extent of migration correlates with the level of secreted SPARC. Our data demonstrated that JPAs expressed SPARC and secreted significantly higher levels than glioblastomas multiforme (GBMs). Vitronectin was absent from well-preserved tumor but present in areas of disrupted tumor, such as degeneration and/or necrosis. SPARC and vitronectin colocalized only in regions of angiogenesis. We observed that the extent of migration on vitronectin inversely correlated with the level of secreted SPARC: the higher the level, the lesser the migration. These data suggest that the outcome of SPARC - ECM interactions may depend on local SPARC concentrations. The high levels of SPARC secreted by the JPAs, paradoxically, may be more prohibitive for migration on vitronectin than the lower levels secreted by the GBMs. This may account, in part, for the lack of JPA invasion into brain tissue along blood vessel membranes.

Adult↗
PubMed2002

P-, E-, and L-selectin mediate migration of activated CD8+ T lymphocytes into inflamed skin.

P- and E-selectin mediate CD4+ Th1 cell migration into the inflamed skin in a murine contact hypersensitivity model. In this model, not only CD4+ T cells but also CD8+ T cells infiltrate the inflamed skin, and the role of CD8+ type 1 cytotoxic T (Tc1) cells as effector cells has been demonstrated. Here we show that in mice deficient in both P- and E-selectin, the infiltration of CD8+ T cells in the inflamed skin is reduced, suggesting the role of these selectins in CD8+ T cell migration. We directly studied the role of selectins using in vitro-generated Tc1 cells. These cells are able to migrate into the inflamed skin of wild-type mice. This migration is partially mediated by P- and E-selectin, as shown by the reduced Tc1 cell migration into the inflamed skin of mice deficient in both P- and E-selectin or wild-type mice treated with the combination of anti-P-selectin and anti-E-selectin Abs. During P- and E-selectin-mediated migration of Tc1 cells, P-selectin glycoprotein ligand-1 appears to be the sole ligand for P-selectin and one of the ligands for E-selectin. P- and E-selectin-independent migration of Tc1 cells into the inflamed skin was predominantly mediated by L-selectin. These observations indicate that all three selectins can mediate Tc1 cell migration into the inflamed skin.

Animals↗
PubMed2004

IL-16 activates plasminogen-plasmin system and promotes human eosinophil migration into extracellular matrix via CCR3-chemokine-mediated signaling and by modulating CD4 eosinophil expression.

Increased eosinophil counts are a major feature of asthmatic airways. Eosinophil recruitment requires migration through epithelium and tissue extracellular matrix by activation of proteases. We assessed the capacity of IL-16, a CD4(+) cell chemotactic factor, to induce migration of eosinophils through a reconstituted basement membrane and evaluated the proteases, mediators, and receptors involved in this migration. IL-16 added to lower chambers of Invasion Chambers elicited eosinophil migration through Matrigel. This effect was decreased by inhibition of the plasminogen-plasmin system (Abs against urokinase plasminogen activator receptor or plasminogen depletion), but not by anti-matrix metalloproteinase-9 Abs. Abs against CD4 also inhibited IL-16-induced eosinophil migration. At the baseline level, few eosinophils (4.6% positive cells with a mean fluorescence of 0.9) expressed surface membrane CD4, while most permeabilized eosinophils (68% positive cells with a mean fluorescence of 18) express the CD4 Ag. TNF-pretreatment increased surface membrane CD4(+) expression by 6-fold as previously described, and increased IL-16-induced cell migration by 2.2-fold. Incubation of eosinophils with IL-16 also increased surface membrane CD4 expression by 5.4-fold, supporting the role of CD4 as receptor for IL-16. Abs against CCR3, eotaxin, or RANTES blocked IL-16-induced migration. In conclusion, IL-16 promotes eosinophil migration in vitro, by activating the plasminogen-plasmin system and increasing the membrane expression of its receptor. This effect is initiated via CD4 and mediated via the release of CCR3 ligand chemokines. Interestingly, most eosinophils express intracellular CD4. Hence, IL-16 may play an important role in the recruitment of blood eosinophils to the bronchial mucosa of asthmatics.

Adult↗
PubMed2005

Sphingosine 1-phosphate receptors regulate chemokine-driven transendothelial migration of lymph node but not splenic T cells.

Chemokines and chemokine receptors are required for T cell trafficking and migration. Recent evidence shows that sphingosine 1-phosphate (S1P) and S1PRs are also important for some aspects of T cell migration, but how these two important receptor-ligand systems are integrated and coregulated is not known. In this study, we have investigated CCL19-CCR7 and CXCL12-CXCR4-driven migration of both splenic and peripheral lymph node (PLN) nonactivated and naive T cells, and used both S1P and the S1PR ligand, FTY720, to probe these interactions. The results demonstrate that splenic T cell migration to CCL19 or CXCL12 is enhanced by, but does not require, S1PR stimulation. In contrast, PLN T cell migration to CXCL12, but not CCL19, requires both chemokine and S1PR stimulation, and the requirement for dual receptor stimulation is particularly important for steps involving transendothelial migration. The results also demonstrate that: 1) splenic and PLN nonactivated and naive T cells use different molecular migration mechanisms; 2) CCR7 and CXCR4 stimulation engage different migration mechanisms; and 3) S1P and FTY720 have distinct S1PR agonist and antagonist properties. The results have important implications for understanding naive T cell entry into and egress from peripheral lymphoid organs, and we present a model for how S1P and chemokine receptor signaling may be integrated within a T cell.

Animals↗