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PubMed2001

The 9-O-acetyl GD3 gangliosides are expressed by migrating chains of subventricular zone neurons in vitro.

Neurons from the anterior subventricular zone (SVZ) of the cerebral cortex migrate tangentially to become interneurons in the olfactory bulb during development and in adult rodents. This migration was defined as neuronophilic, independent of a radial glial substrate. The cortical SVZ and the rostral migratory stream to the olfactory bulb were shown to be rich in 9-O-acetyl GD3 gangliosides (9-O-acGD3), which have been previously shown to be implicated in gliophilic migration in the rodent cerebral cortex and cerebellum. In the present study, we performed SVZ explant cultures using rats during their first postnatal week to analyze the expression of these gangliosides in chain migration of neuronal precursors. We characterized migrating chains of these neuroblasts through morphological analysis and immunocytochemistry for the neural cell adhesion molecule. By using the Jones monoclonal antibody which binds specifically to 9-O-acGD3 we showed that migrating chains from the SVZ explants express 9-O-acGD3 which is distributed in a punctate manner in individual cells. 9-O-acGD3 is also present in migrating chains that form in the absence of radial glia, typical of the neuronophilic chain migration of the SVZ. Our data indicate that 9-O-acetylated gangliosides may participate in neuronophilic as well as gliophilic migration.

Animals↗
PubMed1999

Regulation of rat mesangial cell migration by platelet-derived growth factor, angiotensin II, and adrenomedullin.

This study sought to determine whether platelet-derived growth factor (PDGF) and angiotensin II (AngII) stimulate migration of cultured rat glomerular mesangial cells. After finding that this was so, the effects of adrenomedullin (ADM) and cAMP-elevating agents on basal and stimulated mesangial cell migration were examined. Two isoforms of PDGF, AB and BB, stimulated migration in a concentration-dependent manner between 1 and 50 ng/ml, while the AA isoform lacked significant effect. AngII modestly but significantly stimulated migration in a concentration-dependent manner between 10(-7) and 10(-6) mol/L. Rat ADM significantly inhibited the PDGF BB- and AngII-stimulated migration in a concentration-dependent manner between 10(-8) and 10(-7) mol/L. Inhibition by rat ADM was accompanied by an increase in cellular cAMP. cAMP agonists or inducers such as 8-bromo cAMP, forskolin, and prostaglandin I2 also significantly reduced the stimulated migration. H 89, a protein kinase A (PKA) inhibitor, attenuated the inhibitory effect of ADM, and a calcitonin gene-related peptide (CGRP) receptor antagonist, human CGRP (8-37), abolished the inhibitory effects of rat ADM. These results suggest that PDGF AB and BB as well as AngII stimulate rat mesangial cell migration and that ADM can inhibit PDGF BB- and AngII-stimulated migration, at least in part through cAMP-dependent mechanisms likely to involve specific ADM receptors with which CGRP interacts. The adenylate cyclase/cAMP/PKA system may be involved in the migration-inhibitory effect of ADM in these cells.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2005

Neurotransmitters and chemokines regulate tumor cell migration: potential for a new pharmacological approach to inhibit invasion and metastasis development.

The migration of tumor cells is a prerequisite for tumor cell invasion and metastasis development, which accounts for over 90% of cancer mortality. Therefore a major focus of current tumor biological research is the study of those factors that regulate tumor cell migration. Those chemokines and neurotransmitters that bind to G-protein coupled receptors (also known as serpentine receptors) are the most prominent of these factors. Neurotransmitters have been identified that have not only a stimulatory (e.g. norepinephrine) effect, but an inhibitory effect (e.g. GABA) as well. This is an especially fortuitous development, because many known agonists and antagonists of neurotransmitter receptors are currently being successfully used in the treatment of other pathological conditions (e.g. beta-blockers in the treatment of cardiovascular diseases). Likewise, chemokine receptor antagonists, which are under development for the treatment of HIV or rheumatoid arthritis, may be effective tools for the inhibition of chemokine-driven tumor cell migration as well. A further approach to inhibit tumor cell migration arises from the investigation of the relevant signal transduction pathways. The PKC alpha, for example, is a key enzyme in the regulation of tumor cell migration, but not of leukocyte migration. It thus offers a selective target opportunity for specific pharmacological agents to interfere with tumor cell migration. In this review we therefore summarize the current findings on those serpentine receptors involved in the neurotransmitter- and chemokine-regulated tumor cell migration, on the underlying signal transduction pathways, and on the opportunities to inhibit tumor cell migration and ultimately metastasis development with pharmaceutical agents.

Cell Movement↗
PubMed1986

The effect of steroidal and nonsteroidal anti-inflammatory agents on granulocyte migration into bovine pulmonary artery intimal explants.

To determine whether steroidal or non-steroidal anti-inflammatory agents inhibit granulocyte migration, we measured granulocyte adherence to and migration across the intact endothelial layer of bovine pulmonary artery intimal explants. Explants were placed endothelium uppermost in chemotaxis chamber with either fetal calf serum (FCS) or zymosan activated plasma (ZAP) in medium 199 in the lower well and 5 X 10(6) separated 51Cr labelled granulocytes/ml in medium 199 + FCS in the upper well. Methylprednisolone (0.3 and 3.0 mg/ml), indomethacin (5 and 50 microM) and ibuprofen (10 and 100 microM) were also added to the upper well of some chambers. After 30, 60, 120 or 180 minutes of incubation the chambers were dismantled. Granulocyte adherence was assessed by rinsing the explant in 0.1% trypsin; the number of radioactive counts in the trypsin wash represented the number of adherent cells. Those remaining in the explant represented the number of granulocytes that migrated into the explant. At each time studied, chemotaxin-induced granulocyte migration was 2-3 times that of unstimulated or random migration (180 min incubation with FCS = 30.5% +/- S.E. 2.1; with ZAP in lower well = 61.6 +/- 3.4). Both unstimulated and chemotaxin-induced migration was significantly decreased from 30 minutes by 3.0 mg/ml of methylprednisolone (180 min incubation with ZAP in lower well = 22.3 +/- 5.8), but not by 0.3 mg/ml. However, one hour pretreatment of either the granulocytes or the explant with 3.0 mg/ml methylprednisolone had no significant effect on granulocyte migration. In contrast, granulocyte migration was unaltered by treatment with either indomethacin or ibuprofen. Methylprednisolone, indomethacin and ibuprofen had little effect on granulocyte adherence. We conclude that granulocyte migration across an intact endothelial layer is inhibited by high dose corticosteroids but not by cyclooxygenase inhibitors. This suggests a plausible rationale for use of high doses of corticosteroids in clinical states where granulocytes may mediate tissue injury.

Animals↗
PubMedDate not supplied

Effect of elastase on the directional migration of lung fibroblasts within a three-dimensional collagen matrix.

Interactions between airway epithelial cells and bronchial fibroblasts often require close proximity between these cells. Previous studies have demonstrated that airway epithelial cells direct the migration of lung fibroblasts, but the factors that regulate this process during airway injury are not clear. We hypothesized that exposure of culture substrates to proteolytic enzymes, like those present in the inflamed airway, would increase fibroblast recruitment. We also postulated that elastase might affect the epithelium's ability to attract fibroblasts. We used an in vitro model with fibroblasts embedded between two layers of collagen gel to investigate their migration. Embedded fibroblasts exposed to culture medium alone (baseline) had a slight downward migration (migration directed to the upper gel layer expressed as a percentage of total migration was -2.8 +/- 1.4), but medium supplemented with porcine pancreatic elastase (PPE) resulted in a slight upward migration (2.0 +/- 1.4). When airway epithelial cells were cultured on the upper gel surface, the index of directed migration toward them was 15.9 +/- 1.3. Addition of PPE to the culture medium resulted in a significant increase to 22.3 +/- 1.5 (p < .05). Human neutrophil elastase (HNE) produced similar results, and these effects were inhibited by alpha 1-proteinase inhibitor. Similarly, total fibroblasts per 20 high-powered fields were counted in all conditions, suggesting that mitogenic interactions were not important in this system. The percentage of the total fibroblasts migrating at least 5 microns in any direction was also similar in all groups, suggesting chemokinetic mechanisms were not involved. These data suggest that elastase exposure in a model of the human airway increases directed fibroblast migration through the extracellular matrix. This phenomenon may play a role in the development of subepithelial fibrosis seen in inflammatory airway diseases like asthma.

Animals↗
PubMed1982

Migration of the femoral stem in hip arthroplasties. Analysis of associations with structural, radiological and follow-up variables.

Medical and/or distal migration of the prosthetic stem was found in 63 out of 337 patients (19 per cent) treated surgically with a Christiansen hemiprosthesis, a Christiansen total hip prosthesis or a Charnley total hip prosthesis. Fractured bone cement, radiolucent zones at the cement/bone interface, resorption of the femoral calcar and cortical sclerosis were all associated with migration. Varus position of the Christiansen total hip prosthesis was significantly associated with medical migration, and a short stem was significantly associated with distal migration. The other structural variables could not be linked with migration. Distal migration was pain-inducing and was significantly associated with late infection. Medical migration had a less distinct association with pain, and was not correlated with infection. Both medical and distal migration were time-dependent, and 4 or more years after operation about 2.5 per cent of the prosthetic stems had migrated.

Bone Cements↗
PubMed2001

Molecular determinants of glioma cell migration and invasion.

OBJECT: Migration and invasion are important prerequisites for the infiltrative and destructive growth patterns of malignant gliomas. Infiltrative growth prevents complete tumor resection and causes significant neurological morbidity and mortality. METHODS: The authors assessed the expression of matrix metalloproteinases (MMPs) at messenger RNA and protein levels, MMP-2 and MMP-9 activities, and expression levels of a panel of anti- and proapoptotic proteins of the BCL-2 family. They then correlated their findings with alpha(v)beta3 integrin expression and the migratory and invasive potentials in 12 human malignant glioma cell lines. Multiple MMPs were expressed by most cell lines. The levels of MMP-2 and MMP-3 and the activities of MMP-2 and MMP-9 correlated with tumor cell invasion. Migration and invasion were also correlated. Although the expression levels of alpha(v)beta3 integrin did not predict migration or invasion, a neutralizing alpha(v)beta3 integrin antibody inhibited migration and invasion selectively in cell lines that contained a high level of alpha(v)beta3 integrin expression, thus indicating the important role of alpha(v)beta3 integrin for migration and invasion in this subset of cell lines. An expression pattern of BCL-2 family proteins that favor resistance to apoptosis was associated with enhanced migration, invasion, and MMP activity. Wild-type p53 cell lines migrated farther than mutant p53 cell lines. CONCLUSIONS: Activities of MMP-2 and MMP-9 are the best predictors of glioma cell invasion. The alpha(v)beta3 integrin mediates migration and invasion in a subset of glioma cell lines, but these processes do not depend on alpha(v)beta3 integrin expression. Antiapoptotic BCL-2 family protein expression is a predictor of efficient migration and invasion.

Brain Neoplasms↗
PubMed1995

Effects of macrophage supernatants on mesangial cell migration and hillock formation.

There is considerable evidence suggesting a role for the macrophage (M phi) in the development of glomerulosclerosis (GS) and atherosclerosis, lesions which appear to be analogous. Migration of mesangial cells (MC), which are modified smooth muscle cells, may play a role in the pathogenesis of glomerular injury, and smooth muscle migration may play a role in the pathogenesis of atherosclerosis as well. We undertook the present study to determine the effects of M phi supernatants (M phi SN) on MC migration and formation of MC hillocks, which are considered an in vitro model of GS. By means of a migration assay using wounded cultures of confluent, growth-arrested MC, MC migration was found to be significantly enhanced by incubation with M phi SN at 24 hr (migration score: M phi SN, 24.3 +/- 1.3; control, 11.6 +/- 1.0, P < 0.001) as well as 48 hr incubation (migration score: M phi SN, 34.0 +/- 1.4; control, 15.4 +/- 1.4, P < 0.001). Enhanced MC migration following prolonged incubation with M phi SN was also shown using phase contrast microscopy and scanning electron microscopy. MC hillock formation was enhanced by M phi SN in a concentration-related manner as was hillock size. These data demonstrate that M phi SN can directly enhance MC migration and hillock formation, processes that may in part account for the observed role for the M phi in the development of mesangial expansion and GS as well as atherosclerosis.

Animals↗
PubMed2006

[Migration of bisphenol A and benzophenones from paper and paperboard products used in contact with food].

Migration of bisphenol A (BPA) and benzophenones, i.e., benzophenone (BZ), 4-(dimethylamino)benzophenone (DMAB), Michler's ketone (MK) and 4,4'-bis(diethylamino)benzophenone (DEAB), from 21 paper and paperboard products (15 recycled paperboard boxes and 6 virgin paper products) used in contact with food was examined. Migration levels of compounds from recycled paperboard were compared under various food-simulating conditions. BPA showed the highest migration into 20% ethanol and benzophenones into 95% ethanol. No compounds migrated from virgin paper products, but compounds did migrate into food simulants from recycled paperboard food boxes. BPA migrated into 20% ethanol from all recycled paperboard food boxes between 1.0 and 18.7 ng/mL. Into 95% ethanol, migration of BZ was observed in 8 samples (1.0-18.9 ng/mL), DMAB in 12 samples (1.2-3.7 ng/mL), MK in 13 samples (1.9-9.0 ng/mL), and DEAB in 13 samples (1.0-10.6 ng/mL). The highest migration level was 27.2 ng/mL and most of the migration levels were below 10 ng/mL. These values are sufficiently low compared with the TDI and NOAEL levels. Moreover, the amount of food in daily meals that comes into contact with paperboard products is relatively small. Consequently, it was concluded that there was no safety concern regarding the tested compounds in recycled paperboard food boxes.

Benzhydryl Compounds↗
PubMed2002

Matrix metalloproteinases 9 and 2 are necessary for the migration of Langerhans cells and dermal dendritic cells from human and murine skin.

Dendritic cells migrate from the skin to the draining lymph nodes. They transport immunogenic MHC-peptide complexes, present them to Ag-specific T cells in the T areas, and thus generate immunity. Migrating dendritic cells encounter physical obstacles, such as basement membranes and collagen meshwork. Prior work has revealed that matrix metalloproteinase-9 (MMP-9) contributes to mouse Langerhans cell migration. In this study, we use mouse and human skin explant culture models to further study the role of MMPs in the migration and maturation of skin dendritic cells. We found that MMP-2 and MMP-9 are expressed on the surface of dendritic cells from the skin, but not from other sources. They are also expressed in migrating Langerhans cells in situ. The migration of both Langerhans cells and dermal dendritic cells is inhibited by a broad spectrum inhibitor of MMPs (BB-3103), by Abs to MMP-9 and -2, and by the natural tissue inhibitors of metalloproteinases (TIMP), TIMP-1 and TIMP-2. Inhibition by anti-MMP-2 and TIMP-2 define a functional role for MMP-2 in addition to the previously described function of MMP-9. The importance of MMP-9 was emphasized using MMP-9-deficient mice in which Langerhans cell migration from skin explants was strikingly reduced. However, MMP-9 was only required for Langerhans cell migration and not maturation, since nonmigrating Langerhans cells isolated from the epidermis matured normally with regard to morphology, phenotype, and T cell stimulatory function. These data underscore the importance of MMPs, and they may be of relevance for therapeutically regulating dendritic cell migration in clinical vaccination approaches.

Animals↗
PubMed2005

A sonographic assessment of different patterns of placenta previa "migration" in the third trimester of pregnancy.

OBJECTIVE: The purpose of this study was to compare the rates and patterns of placental "migration" with the mode of fetal and placental delivery and the incidence of peripartum complications. METHODS: This was a retrospective study of 163 cases of placenta previa diagnosed by transvaginal sonography at 28 weeks' gestation that were followed serially by sonography. The patients were stratified into 3 groups depending on the placenta-to-internal cervical os distance: (1) an overlap of 0.0 cm or greater over the cervical os, (2) 0.1 to 2.9 cm, and (3) 3.0 cm or greater. The mean rate of placental migration (millimeters per week) was obtained at 28 to 32 and 32 to 36 weeks' gestation. A pattern of placental migration was classified as one with acceleration or deceleration of the placental migration in the late third trimester based on a comparison between the migration rates at 28 to 32 and 32 to 36 weeks' gestation. RESULTS: At the time of delivery, 22, 29, and 112 patients were included in groups 1, 2, and 3, respectively. The rates of placental migration correlated with the final placental distance from the internal cervical os (0.1 to 4.1 mm/wk for groups 1 and 3, respectively). Significantly higher rates of interventional cesarean delivery (CD) (P=.0002), elective CD (P=.0254), manual placenta removal (P=.0419), and placenta accreta (P=.0039), but not CD for indications other than placenta previa (P=.0752), were associated with a placental distance of less than 2.0 cm away from the cervix and a deceleration pattern of placental migration. In contrast, vaginal delivery was significantly associated with a placental distance of 2.0 cm or greater away from the cervix and an acceleration pattern of placental migration (P=.0034). CONCLUSIONS: A final placental distance of less than 2.0 cm from the internal cervical os and a deceleration pattern of placental migration were significantly associated with an interventional CD and a higher rate of peripartum complications.

Delivery, Obstetric↗
PubMed1999

Migration of langerhans cells and dermal dendritic cells in skin organ cultures: augmentation by TNF-alpha and IL-1beta.

Migration from sites of antigen encounter to lymphoid organs is essential to the strong immunogenic function of dendritic cells (DC). In the skin, migration proceeds through dermal lymphatic vessels and is regulated in an incompletely understood way by inflammatory mediators. We studied the effects of tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in mouse skin organ cultures by direct enumeration of migrating DC and by immunohistochemistry. (1) Neutralizing antibodies to TNF-alpha and IL-1beta inhibited migration of DC, also in human skin explants (TNF-alpha). (2) TNF-alpha at low concentrations (50 U/mL) and IL-1beta (50-3000 U/mL) augmented migration to about 150% of spontaneous migration. (3) High concentrations of TNF-alpha (5000 U/mL) inhibited migration by approximately 50%. (4) DC migration from skin explants of TNF-alpha/lymphotoxin-alpha double-deficient mice and TNF-receptor type 1 and 2 double knockout mice was not impaired. (5) TNF-alpha effects were neutralized by anti-IL-1beta, and vice versa. We conclude that in normal animals both TNF-alpha and IL-1beta are required for DC migration to occur. In the complete absence of one cytokine (TNF-alpha), however, backup mechanisms step in.

Animals↗
PubMed1999

Decorin inhibits cell migration through a process requiring its glycosaminoglycan side chain.

Several studies overwhelmingly support the notion that decorin (DCN) is involved in matrix assembly, and in the control of cell adhesion and proliferation. However, nothing is known about the role of DCN during cell migration. Cell migration is a tightly regulated process which requires both adhesion (at the leading edge of the cell) and de-adhesion (at the trailing edge of the cell) from the substratum. We have determined in this study the effect of DCN on MG-63 osteosarcoma cell migration and have analyzed whether its effect is mediated by the protein core and/or the glycosaminoglycan side chain. DCN impeded the migration-promoting effect of matrix molecules (fibronectin, collagen type I) known to interact with the proteoglycan. Conversely, DCN did not counteract the migration-promoting effect of fibrinogen lacking proteoglycan affinity. DCN bearing dermatan-sulfate chains (i.e., skin and cartilage DCN) was about 20-fold more effective in inhibiting cell migration than DCN bearing chondroitin-sulfate chains (i.e., bone DCN). In addition, chondroitinase AC-treatment of cartilage DCN (which specifically removes chondroitin-sulfate chains) did not attenuate the inhibitory effect of this proteoglycan, while cartilage DCN deprived of both chondroitin- and dermatan-sulfate chains failed to alter cell migration promoted by either fibronectin or its heparin- and cell-binding domains. These data assert that the dermatan-sulfate chains of DCN are responsible for a negative influence on cell migration. However, isolated glycosaminoglycans failed to alter cell migration promoted by fibronectin, indicating that strongly negatively charged glycosaminoglycans alone cannot account for the impaired cell motility seen with DCN. Overall, these results show that the inhibitory action of DCN is dependent of substratum binding, is differentially mediated by its glycosaminoglycan side chains (chondroitin-sulfate vs. dermatan-sulfate chains), and is independent of a steric hindrance effect exerted by its glycosaminoglycan side chains.

Animals↗
PubMed1975

An explanation of the apparent reversal of the circadian migration by Hymenolepis diminuta (Cestoda) in the rat.

Hymenolepis diminuta exhibits 2 concurrent migrations: an age-dependent, forward migration and a circadian migration. In experiments where the age of worms was assumed to be uniform throughout the test-day, 2 patterns (7-day-old and 16-day-old) of circadian migration were seen and an apparent reversal in circadian pattern suggested. In experiments where the age of worms became progressively older during the test-day, only the 16-day-old pattern was seen and no reversal was observed. The 7-day-old pattern and hence the apparent reversal in circadian migration is postulated to be an artifact of the method whereby both the age and size of worms were presumed to be uniform throughout the test-day. The 7-day-old pattern results from comparing worms of unequal size and thus at different positions in their forward migration. Data on the daily variation of stomach contents of rats and the results from protein determinations of 6-day-old worms support this hypothesis. Therefore H. diminuta is believed to exhibit only the 16-day-old pattern of circadian migration: an anterior migration between 12 midnight and 6 AM, and a posterior migration between 12 noon and 6 PM.

Age Factors↗
PubMed2002

A pivotal role for CC chemokine receptor 5 in T-cell migration to tumor sites induced by interleukin 12 treatment in tumor-bearing mice.

Interleukin (IL) 12 treatment in the CSA1M and OV-HM, but not in Meth A tumor models,induces tumor regression that is associated with T-cell migration to tumor sites.Here, we investigated the role of the CC chemokine receptor (CCR)5 in T-cell migration induced after IL-12 treatment. In the two IL-12-responsive tumor models (CSA1M and OV-HM), IL-12 treatment up-regulated the mRNA expression of CCR5 in splenic T cells as well as ligands for CCR5, such as macrophage inflammatory protein (MIP) 1alpha and MIP-1beta in tumor masses. In contrast, the expression of CCR5 in spleens and MIP-1alpha/MIP-1beta in tumor masses was marginally induced before and even after IL-12 treatment in the Meth A model in which T-cell migration is not observed. T cells infiltrating tumor masses in the former two IL-12-responsive models expressed CCR5. Administration of a synthetic CCR5 antagonist TAK-779 to tumor-bearing mice during IL-12 immunotherapy prevented T-cell migration and tumor regression. Furthermore, anti-CCR5 antibody was found to inhibit T-cell migration in the lymphoid cell migration assay. Namely, although splenic T cells prepared from IL-12-treated CSA1M or OV-HM-bearing mice migrated into the corresponding tumor masses in recipient mice, the migration was inhibited when donor T cells were treated with anti-CCR5 antibody before the injection. These results indicate a critical role for CCR5 in the induction of T-cell migration to tumor sites after IL-12 treatment.

Amides↗
PubMed2002

Endothelial Rho and Rho kinase regulate neutrophil migration via endothelial myosin light chain phosphorylation.

The transendothelial migration of neutrophils is a critical step in acute inflammation, which we previously showed to be regulated by endothelial myosin light chain (MLC) kinase. Recent studies suggest that Rho and Rho kinase are also key mediators of MLC phosphorylation, but their roles in neutrophil migration have not been investigated. In the present study, a transwell chamber migration assay system incorporating endothelial monolayer was used to examine the numbers of migrating neutrophils, endothelial F-actin and myosin II rearrangement, and endothelial MLC phosphorylation at selected times during the neutrophil migration in vitro. The results showed that pretreating endothelial cells with C3 (Rho inhibitor) or Y-27632 (Rho kinase inhibitor) significantly diminished neutrophil migration, actin polymerization, myosin II filament formation, and MLC phosphorylation normally associated with the migration. These data suggest that endothelial Rho and Rho kinase regulate transendothelial neutrophil migration by modulating the cytoskeletal events that mediate such migration.

Actins↗
PubMed2003

Distinguishing between directional guidance and motility regulation in neuronal migration.

Although neuronal migration is an essential process in development, how neural precursors reach their final destination in the nervous system is not well understood. Secreted molecules that are known to be involved in axon guidance are likely to play important roles in regulating neuronal migration, but an important issue that remains unclear is whether such molecules act as directional guidance cues or as motility regulators in neuronal migration. The secreted protein Slit was initially suggested to be a repellent for migrating neurons (Wu et al., 1999). However, it was concluded recently that Slit plays an inhibitory rather than a repulsive role in neuronal migration (Mason et al., 2001). We have developed a series of assays that allow us to differentiate between repulsive and inhibitory effects of secreted molecules, and we demonstrate that Slit is a repellent capable of reversing the direction of neurons migrating either in culture or in their native pathways. We also show that although Slit reduces migratory speed under certain conditions, it can function as a repellent without concurrent inhibition of neuronal migration. This is the first study to clearly demonstrate that migrating neurons can be directionally guided by secreted molecules. These findings provide a basis to understand the physiological roles of secreted molecules in the developing nervous system and have implications on how they could be applied therapeutically. Our results also indicate that it should be possible to determine the specific action of other molecules as directional guidance cues or as motility regulators of cell migration.

Animals↗
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↗