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The wax and wane of interstate migration patterns in the U.S.A. in the 1980s: a demographic effectiveness field perspective.

The author analyzes the structure of temporal changes in U.S. internal migration over the period 1980-1988 using data from matched income tax returns. "A number of hypotheses are explored about how in-migration and out-migration fields wax and wane, thereby giving rise to the overall shifts in demographic effectiveness measured over the period. The results highlight the characteristics of recent (1980-88) shifts in U.S. internal migration patterns including net migration reversals from strong net in-migration to strong net out-migration for states with significant energy sectors, the stanching of net out-migration from many states of the American manufacturing belt, the turnaround to net in-migration for all of northern New England, and the continuance of highly effective net in-migration to the sunbelt states of Florida, Arizona, and Nevada."

Americas↗

Regulation of lymphocyte motility by macrophages: characterization of a lymphocyte migration inhibitory factor derived from a macrophage-like cell line.

An inhibitory factor on lymphocyte migration was detected using a capillary random migration assay in the culture supernatant of peritoneal exudate macrophages cultured at concentrations greater than 8 x 10(6) cells/ml. After examining different macrophage-like cell lines, J774A.1 cells were found to produce this inhibitory factor, which was termed lymphocyte migration inhibitory factor (LMIF). The inhibitory effect of LMIF on the migration of spleen lymphocytes, thymocytes, and bone marrow cells was determined. The migration of thymocytes was more sensitive to LMIF than was the migration of spleen lymphocytes and bone marrow cells. Interestingly, when the effect of LMIF was tested on the migration of spleen T cells and B cells, T cells were more sensitive than B cells. When the thymocytes were separated by peanut agglutinin into mature and immature thymocytes, the migration of mature thymocytes was more sensitive than that of immature thymocytes, the migration of mature thymocytes was more sensitive than that of immature thymocytes to the effect of LMIF, suggesting that the greatest effect of LMIF was on the migration of mature T cells. Partial purification of LMIF by ion-exchange and gel-filtration chromatography revealed that it is approximately 14,000 in molecular weight and could exist in either monomeric or dimeric forms. The possible role of this factor in an immune response is discussed.

Animals↗

Migration of prostate brachytherapy seeds to the vertebral venous plexus.

PURPOSE: We report two cases of seed migration to the vertebral venous plexus after iodine-125 (I-125) transperineal interstitial permanent prostate brachytherapy. METHODS AND MATERIALS: Case 1: A 67-year-old Japanese man underwent percutaneous transperineal interstitial permanent prostate brachytherapy at our institution. Three months after brachytherapy, routine followup kidney-urinary bladder (KUB) radiography showed two seeds that had migrated to the pelvic area and were overlapped by sacral bone. It was very difficult to detect the seeds by visceral CT, because seeds were in contact with to vertebral bone, and seeds and bone were of the same CT value in visceral CT. But bone CT could distinguish seeds and bone, and it showed seed migration to the vertebral venous plexus in the sacral vertebral canal. Case 2: A 75-year-old Japanese man underwent percutaneous transperineal interstitial permanent prostate brachytherapy at our institution. The day after seed implantation, routine followup KUB radiography showed that a seed had migrated to the pelvic area and was overlapped by sacral bone. Bone CT clearly showed seed migration to the vertebral venous plexus in the vertebral canal in comparison with visceral CT. RESULTS: Seeds that have migrated to the vertebral venous plexus are difficult to be detected by visceral CT or KUB radiography. In visceral CT, it is difficult to distinguish seed and bone, especially when they are touching each other because they have the same CT value in visceral CT. It is therefore necessary to perform bone CT to detect such migrating seeds. CONCLUSIONS: To our knowledge, this is the first report of seed migration to the vertebral venous plexus after prostate brachytherapy. We thought that seeds migrate to the vertebral plexus via the pelvic venous pathway. If seed migration to the pelvic area and the overlapped sacral bone area is found after brachytherapy, bone CT should be performed, especially when it is difficult to detect the seed in visceral CT.

Adenocarcinoma↗

Incidence and risk factors for biliary and pancreatic stent migration.

Endoprostheses are commonly used in the treatment of biliary and pancreatic disorders. The frequency of and potential risk factors for stent migration, however, remain largely unknown. From January 1986 to June 1990, 807 biliary and pancreatic stents were placed at our institution. Our study analyzed the occurrence of stent migration among the 589 stents for which follow-up data were available. Results demonstrated incidence rates of 4.9 and 5.9% for proximal (into the duct) and distal (out of the duct) biliary stent migration, respectively. Likewise, incidence rates of 5.2 and 7.5% were observed for proximal and distal pancreatic stent migration, respectively. Malignant strictures, larger diameter stents, and shorter stents were significantly associated with proximal biliary stent migration. Sphincter of Oddi dysfunction and longer stents were associated with proximal pancreatic stent migration. Migration of stents out of the common bile duct occurred more frequently in papillary stenosis. No other significant risk factors for distal migration were found. These results indicate that stent migration is an important complication. Multiple risk factors were associated with stent migration and need to be considered in the development of new stent types.

Common Bile Duct↗

Migration of silicone through the fibrous capsules of mammary prostheses.

The usual reaction of the human body to implantation of a silicone prosthesis is formation of a fibrous capsule. Local reactions to silicone outside this fibrous capsule and distant migration of silicone particles have been described. So far, transcapsular migration of silicone particles from the mammary implant through the fibrous capsule of mammary prostheses has not been studied. In this prospective study 71 capsules found in 40 patients were histologically studied. The chi-squared test was applied to evaluate a possible correlation between silicone migration on the one hand and implant age and integrity of the prostheses on the other. The degree of silicone migration was discerned in four stages. Stage 1 represents no silicone particles in the capsule, stage 2 represents migration up to less than half of the capsule thickness, stage 3 shows migration confined to the outer half of the capsule thickness, and stage 4 means transcapsular silicone migration. In only 4 of 71 capsules no migration into or through the capsule was observed. The degree of silicone migration was significantly less in patients in whom the capsule was calcified and was significantly more in patients in whom implantation exceeded 12 years. There was no significant correlation between the status of the prosthesis (intact, bleeding, or ruptured) and the degree of silicone migration.

Adult↗

Borrelia burgdorferi and interleukin-1 promote the transendothelial migration of monocytes in vitro by different mechanisms.

A prominent feature of Lyme disease is the perivascular accumulation of mononuclear leukocytes. Incubation of human umbilical vein endothelial cells (HUVEC) cultured on amniotic tissue with either interleukin-1 (IL-1) or Borrelia burgdorferi, the spirochetal agent of Lyme disease, increased the rate at which human monocytes migrated across the endothelial monolayers. Very late antigen 4 (VLA-4) and CD11/CD18 integrins mediated migration of monocytes across HUVEC exposed to either B. burgdorferi or IL-1 in similar manners. Neutralizing antibodies to the chemokine monocyte chemoattractant protein 1 (MCP-1) inhibited the migration of monocytes across unstimulated, IL-1-treated, or B. burgdorferi-stimulated HUVEC by 91% +/- 3%, 65% +/- 2%, or 25% +/- 22%, respectively. Stimulation of HUVEC with B. burgdorferi also promoted a 6-fold +/- 2-fold increase in the migration of human CD4(+) T lymphocytes. Although MCP-1 played only a limited role in the migration of monocytes across B. burgdorferi-treated HUVEC, migration of CD4(+) T lymphocytes across HUVEC exposed to spirochetes was highly dependent on this chemokine. The anti-inflammatory cytokine IL-10 reduced both migration of monocytes and endothelial production of MCP-1 in response to B. burgdorferi by approximately 50%, yet IL-10 inhibited neither migration nor secretion of MCP-1 when HUVEC were stimulated with IL-1. Our results suggest that activation of endothelium by B. burgdorferi may contribute to formation of the chronic inflammatory infiltrates associated with Lyme disease. The transendothelial migration of monocytes that is induced by B. burgdorferi is significantly less dependent on MCP-1 than is migration induced by IL-1. Selective inhibition by IL-10 further indicates that B. burgdorferi and IL-1 employ distinct mechanisms to activate endothelial cells.

Amnion↗

Novel protein kinase C and matrix metalloproteinase inhibitors of vegetable origin as potential modulators of Langerhans cell migration following hapten-induced sensitization.

BACKGROUND: Migration and maturation of epidermal dendritic cells, the Langerhans cells (LC), are central events in the initiation of the cutaneous immune response. LC migration from skin to draining lymph nodes is regarded as an indispensable step for the early phase of antigen-specific sensitization. Among the several agents which influence the ability of LC to migrate, previous studies have revealed that matrix metalloproteinases (MMPs) and protein kinase C (PKC) contribute to promoting LC migration. In this work, we studied the effect of two recently developed PKC and MMPs inhibitors of vegetable origin on the migration of in vitro activated LC. METHODS: The migratory capacity of epidermal and in vitro generated LC was assessed using a reconstituted basement membrane assay (Matrigel), mimicking the prerequisite passage through the dermal-epidermal basement membrane on the way to the lymph nodes. RESULTS: Contact with chemical allergens, Bandrowski's base or 2,4-dinitrobenzenesulfonic acid (DNBS), triggered migration. In the presence of PKC inhibitors, D-erythro-sphingosine and OX100, or an inhibitor of MMPs, LU105, allergen-induced migration of LC was strongly decreased. The association between OX100 and LU105 was more efficient in modulating the migration of activated LC compared to each molecule tested separately. CONCLUSIONS: These results showed that PKC and MMPs inhibitors act in synergy to inhibit the migration of activated epidermal dendritic cells in vitro. They underscore the role of PKC and MMPs inhibitors and suggest they may be of relevance for therapeutically regulating epidermal dendritic cell migration in inflammatory dermatoses.

Antigens, CD↗

Modulation of the random migration of human platelets.

Random migration of human platelets has been recognized as a parameter of platelet function which can be assessed in a reproducible manner by modification of the Boyden micropore filter technique for evaluating this function in other cells (Boyden, S. 1962. J. Exp. Med. 115: 453-466). Because platelets are extremely susceptible to aggregation, the conditions for collecting and isolating platelets and the migration buffer (Ca(++) and Mg(++)-free phosphate buffered saline, pH 6.8, with glucose and gelatin) were selected to minimize such a possibility. The random movement of platelets into the micropore filter was maximal at 30-37 degrees C and was contingent upon the metabolic integrity of the cell; thus, it can be attributed to active spontaneous migration. While the initiating and enhancing effects of epinephrine on the platelet aggregation-release reaction are mediated by an alpha-adrenergic receptor, the inhibition of random migration involved a beta-receptor. Equimolar propranolol but not phentolamine prevented epinephrine inhibition of random migration, and isoproterenol had activity comparable to epinephrine while phenylephrine was inactive. The capacity of the cholinomimetic agent, carbachol, to increase platelet migration is reminiscent of the recent findings in several cell systems in which beta-adrenergic and cholinergic stimuli have opposite effects. The prostaglandins E1 and E2 augmented spontaneous migration in contrast to their well established inhibitory action on platelet aggregation at the concentrations employed. The suppression by indomethacin of prostaglandin enhancement and of spontaneous migration implies a requirement for the prostaglandin biosynthetic pathway during the migration process. Thus, the spontaneous migration of human platelets, an additional parameter of platelet function for in vitro investigations, disclosed not only a beta-adrenergic receptor for epinephrine, but also a capacity for cholinergic augmentation and an apparent requirement for prostaglandin biosynthesis.

Blood Platelets↗

Periodontal conditions of teeth presenting pathologic migration.

The aim of the present study was to evaluate the periodontal conditions of anterior teeth that presented pathologic migration in patients with chronic periodontitis and to compare periodontal destruction in migrated versus non-migrated teeth. The sample included 32 patients of both sexes (mean age: 46.0 +/- 11.6 years) diagnosed with generalized chronic periodontitis and selected on the basis of the presence of pathologic migration in one or more anterior teeth. This migration was classified according to the following categories: facial flaring, diastema, proximal tilting, rotation or extrusion. The periodontal parameters recorded were clinical attachment loss (CAL) and percentage of radiographic bone loss (BL). Mean CAL of 5.50 +/- 2.20 mm and mean BL of 41.90 +/- 15.40% were found in 115 teeth assessed. The most frequent type of migration was facial flaring (34.80%), followed by diastema (27.00%). Extrusion was hardly observed in the sample (4.30%). However, greater severity of BL and CAL were observed in teeth with this type of migration (59.44% and 8.42 mm, respectively), and in teeth with facial flaring (45.17% of BL and 6.07 mm of CAL). Kruskal-Wallis test indicated that BL presented by teeth with extrusion or facial flaring was greater than that observed in rotated or tilted teeth (p < 0.05), while there was no difference between groups regarding CAL (p = 0.11). It was observed that anterior teeth with pathologic migration presented greater CAL and BL (5.1 mm and 40%) than non-migrated teeth (4.1 and 31%). The study indicated that the most prevalent kind of pathologic migration is facial flaring, which was associated to higher level of bone loss.

Alveolar Bone Loss↗

An examination of regional migration patterns in Mexico: new and old Mexican regions.

This paper examines Mexican regional patterns. Different regional definitions are utilized to examine in-/out-migration patterns in 4 different periods: 1) 1979-1980, 2) 1975-1979, 3) prior to 1975, and 4) lifetime. 5 regional definitions previously used to delineate state level Mexican regions were compared to new regions by a maximum likelihood clustering technique. Previously defined regions do not compare with the empirically delineated regions developed by the cluster analysis. A cluster analysis of in-/out-migration patterns suggests the following: 1) distinct in-/out-migration patterns for both short- and long-term migration patterns, 2) a central region consisting of Mexico and the Federal District having its own distinct regional characteristics for both in-/out-migration patterns, particularly intraregional migration among those 2 states exceeds any other interregional migration patterns, and 3) the unique role played by Jalisco in mediating long-term inflows prior to 1975, and since 1975, out-migration from the same state. Previous research rarely identified the Central region consisting of Mexico and the Federal District. Using net migration for interregional migration analysis may possibly be misleading since immigration and out-migration phenomena show distinct patterns of geographic mobility at the state level, and such regional differences are consistent for the 4 migration periods. A careful analysis accounting for both distinct migration patterns in the Central region and different patterns in in-/out-migration are necessary to obtain an understanding of regional migration patterns in Mexico.

Americas↗

[Radiological study of the migration of prosthetic implants following hip arthroplasty].

Migration of the acetabular and femoral implants after THR is a better index of the stability of the bone-implant interfaces than are clinical or radiological results. Roentgenstereophotogrammetry (RSA) studies 3-D migration of the implants with high accuracy (0.15 to 0.28 mm for linear migrations). RSA presents several drawbacks which restrict its use to prospective studies on small numbers of patients. Simpler methods have therefore been developed to assess 2-D migration on standard films in retrospective studies. The precision of these "simple" methods is limited, due to several factors: the difficulty to define reliable landmarks on femur or pelvis, sometimes even on implants, measurement errors, related to variations in radiographic technique (focal distance, beam centering, patient positioning). Sutherland, Wetherell and Nunn have proposed methods with an accuracy around 2-3 mm. It appears impossible to correct migration measurements for distorsions due to patient positioning; the EBRA method was therefore developed to reject non-comparable films using a comparability algorithm. A precision of 0.20 to 0.32 mm can thus be reached for the study of cup migration. The same pitfalls are encountered in assessment of migration of the femoral implant; a preliminary theoretical study is mandatory for every implant studied. The data presently available show that migration at 2 years is predictive of the long-term evolution of an implant; for the cup, migration of 1 mm or more at 2 years is predictive of late failure, and similar conclusions can be drawn regarding the femoral implant. The 2-D assessment of implant migration using a correct "simple" method provides a mean to evaluate a new implant or an innovative technical modification in a reasonable amount of time, on a limited number of patients.

Acetabulum↗

Matrix-mesangial cell interaction modulates migration of macrophages.

BACKGROUND: Macrophages (Møs) have been demonstrated to play an important role in immune-mediated renal injury. Accumulation of macrophages in the mesangium has been reported to be a key event in the development of focal glomerulosclerosis. We hypothesized that mesangial cells (MCs) and matrix interaction may be a determinant for the migration of Møs into the mesangium. Therefore, we studied the effect of the interaction between matrix and MCs on the migration of Møs. METHODS: Mouse MCs were plated on Petri dishes coated either with buffer, collagen type I, III, IV, or Matrigel in media containing 1% fetal calf serum for 48 hours. Subsequently, supernatants were collected and stored. The effect of these supernatants (conditioned media) was evaluated on the migration of Møs across a filter in a modified Boyden chamber. RESULTS: Conditioned media from MCs grown on Matrigel (MC-Matrigel interaction products, MC-MGP) enhanced the migration of macrophages across a filter in a modified Boyden chamber when compared with conditioned media from MCs grown on plastic, collagen type I, type III, or type IV (MC-PP, MC-CI, MC-CIII, and MC-CIV). MC-MGP enhanced the migration of Møs in a dose dependent manner. Anti-MCP-1 antibodies attenuated (P < 0.05) the MC-MGP-induced Mø migration (MC-MGP, 16.8 +/- 2.5 vs MC-MGP + anti-MCP-1 antibody, 6.5 +/- 1.2 migrated macrophages/field, n = 12). Anti-TGF-beta antibodies did not attenuate MC-MGP-induced Mø migration. MCs grown on Matrigel showed a 5-fold increase of MCP-1 mRNA when compared with cells grown on plastic or collagen type IV. CONCLUSIONS: The present study suggests that matrix components may modulate the migration of Møs. This effect of MC-matrix interaction on macrophage migration may be mediated through the generation of MCP-1.

Animals↗

Migration of multiple sclerosis lymphocytes through brain endothelium.

CONTEXT: T-lymphocyte migration through the blood-brain barrier is a central event in the process of lesion formation in multiple sclerosis (MS). OBJECTIVES: To assess the ability of lymphocytes derived from the peripheral blood of patients with clinically active and inactive MS to migrate across an artificial model of the blood-brain barrier and to elucidate the molecular mechanisms involved in such a process. DESIGN: We developed an in vitro model of lymphocyte migration using a Boyden chamber coated with a monolayer of human brain microvascular endothelial cells. RESULTS: The rates of migration of lymphocytes obtained from patients with acutely relapsing and active secondary progressive MS was significantly increased compared with those obtained from healthy controls and patients with inactive secondary progressive disease. Ribonuclease protection assays and enzyme-linked immunosorbent assays indicated that monocyte chemoattractant protein 1 and interleukin 8 were the major chemokines produced by brain endothelial cells grown under the culture conditions used for the migration assays. The rate of migration of the MS lymphocytes could be inhibited by 60% with an antimonocyte chemoattractant protein 1 monoclonal antibody, indicating a functional role for this chemokine in the migration process. In agreement with previous reports, we found that the tissue inhibitor of metalloproteinase 1, a matrix metalloproteinase inhibitor, also reduced migration of MS lymphocytes by 50%. CONCLUSIONS: The results demonstrate an increased migration rate of MS T lymphocytes across the brain endothelium barrier and that such migration is dependent on chemokine monocyte chemoattractant protein 1 and on matrix metalloproteinases.

Adult↗

Cyclic 3',5'-adenosine monophosphate modulates retinal pigment epithelial cell migration in vitro.

Retinal pigment epithelial (RPE) cell migration has been implicated in the pathogenesis of proliferative vitreoretinopathy (PVR). Using a modified Boyden chamber assay, we have examined the effect of cyclic nucleotides on human RPE cell migration in vitro. Dibutyryl cyclic 3',5'-adenosine monophosphate (cAMP) (10(-3) mmol/L) inhibits RPE cell random migration by 83%, fibronectin-induced chemotaxis by 61%, and platelet-derived growth factor-induced chemotaxis by 68%. Random and directed migration of RPE cells is not significantly affected by 8-bromo cyclic 3',5'-guanosine monophosphate. Agents that significantly increase intracellular levels of cAMP are also inhibitors of RPE cell migration. Though there is a fairly good correlation for most drugs for their ability to stimulate cAMP production and their ability to inhibit cell migration, it is not perfect, suggesting that some drugs may modulate migration by more than one mechanism. Timolol blocked both the isoproterenol-induced stimulation of RPE adenylate cyclase and attenuated the ability of isoproterenol to inhibit RPE migration. These data suggest that cAMP may modulate RPE cell migration in an inhibitory fashion. Elucidation of the biochemical events involved in RPE cell migration could provide information that might be useful in planning a strategy to attempt pharmacologic control of proliferative vitreoretinopathy.

Adenylyl Cyclases↗

Novel metal-to-metal silyl-migration reactions in heterometallic complexes.

An unprecedented, intramolecular metal-to-metal silyl ligand migration reaction has been discovered in a series of phosphido-bridged iron-platinum complexes and which may be triggered by an external nucleophile. Thus, reaction of solutions of [(OC)3-(R1/3Si)Fe(mu-PR2R3)Pt(1,5-COD) (1a R1 = OMe, R2 = 3 = Ph; 1b R1 = OMe, R2 = R3 = Cy; 1c R1 = Ph, R2 = R3 = Ph; 1d R1 = Ph, R2 = R3 = Cy; 1e R1 = Ph, R1 = H, R3 = Ph) in CH2Cl2 with CO rapidly afforded the corresponding complexes [(OC)4Fe(mu-PR2R3)Pt(SiR1/3)-(CO)] (2a-e) in which the silyl ligand has migrated from Fe to Pt, while two CO ligands have been ligated, one on each metal. When 1a or 1c was slowly treated with two equivalents of tBuNC at low temperature, quantitative displacement of the COD ligand was accompagnied by silyl migration from Fe to Pt and coordination of an isonitrile ligand to Fe and to Pt to give [(OC)3-(tBuNC)Fe(mu-PPh2)Pt[Si(OMe)3](CNtBu)] (3a) and [(OC)3(tBuNC)-Fe(mu-PPh2)Pt[SiPh3](CNtBu)] (3c). Reaction of 2a with one equivalent of tBuNC selectively led to substitution of the Pt-bound CO to give [(OC)4-Fe(mu-PCy2)Pt[Si(OMe)3](CNtBu)] (4b), which reacted with a second equivalent of tBuNC to give [(OC)4Fe(mu-PCy2)-Pt[Si(OMe)3](CNtBu)2] (5b) in which the metal-metal bond has been cleaved. Opening of the Fe-Pt bond was also observed upon reaction of 3a with tBuNC to give [(OC)3(tBuNC)-Fe(mu-PPh2)Pt[Si(OMe)3](CNtBu)2] (6). The silyl ligand migrates from Fe, in which it is trans to mu-PR2R3 in all the metal-metal-bonded complexes, to a position cis to the phosphido bridge on Pt. However, in 5a,b and 6 with no metal-metal bond, the Pt-bound silyl ligand is trans to the phosphido bridge. The intramolecular nature of the silyl migration, which may be formally viewed as a redox reaction, was established by a cross-over experiment consisting of the reaction of 1a and 1d with CO; this yielded exclusively 2a and 2d. The course of the silyl-migration reaction was found to depend a) on the steric properties of the -SiR1/3 ligand, and for a given mu-PR2R3 bridge (R2 = R3 = Ph), the migration rate decreases in the sequence Si(OMe)3> SiMe2Ph> SiMePh2>>SiPh3; b) on the phosphido bridge and for a given silyl ligand (R1 = OMe), the migration rate decreases in the order mu-PPh2 >> mu-PHCy; c) on the external nucleophile since reaction of 1c with two equivalents of P(OMe)3, P(OPh)3 or Ph2PCH2C(O)Ph led solely to displacement of the COD ligand with formation of 11a-c, respectively, whereas reaction with two equivalents of tBuNC gave the product of silyl migration 3c. Reaction of [(OC)3-[(MeO)3Si]Fe(mu-PPh2)Pt(PPh3)2] (7a) with tBuNC (even in slight excess) occurred stereoselectively with replacement of the PPh3 ligand trans to mu-PPh2, whereas reaction with CO led first to [(OC)3((MeO)3Si)Fe(mu-PPh2)Pt(CO)-(PPh3)] (8a), which then isomerized to the migration product [(OC)4Fe(mu-PPh2)Pt[Si(OMe)3](PPh3)] (9a). Most complexes were characterized by elemental analysis, IR and 1H, 31P, 13C, and 29Si NMR spectroscopy, and in five cases by X-ray diffraction.

Journal Article↗

Cyclic AMP-dependent protein kinase A plays a role in the directed migration of human keratinocytes in a DC electric field.

Skin wound healing requires epithelial cell migration for re-epithelialization, wound closure, and re-establishment of normal function. We believe that one of the earliest signals to initiate wound healing is the lateral electric field generated by the wound current. Normal human epidermal keratinocytes migrate towards the negative pole, representing the center of the wound, in direct currents of a physiological strength, 100 mV/mm. Virtually nothing is known about the signal transduction mechanisms used by these cells to sense the endogenous electric field. To elucidate possible protein kinase (PK) involvement in the process, PK inhibitors were utilized. Two important findings have been described. Firstly, addition of 50 nM KT5720, an inhibitor of PKA, resulted in a 53% percent reduction in the directional response of keratinocytes in the electric field, while not significantly affecting general cell motility. The reduction was dose-dependent, there was a gradual decrease in the directional response from 5 to 50 nM. Secondly, addition of 1 microM ML-7, a myosin light chain kinase inhibitor, resulted in an approximate 31% decrease in the distance the cells migrated without affecting directional migration. The PKC inhibitors GF109203X at 4 microM and H-7 at 20 microM and W-7, a CaM kinase inhibitor, did not significantly alter either directed migration or cell migration, although they all resulted in a slight reduction in directional migration. D-erythro-sphingosine at 15 microM, a PKC inhibitor, had virtually no effect on either migration distance or directed migration. These findings demonstrate that divergent kinase signaling pathways regulate general cell motility and sustained directional migration and highlight the complexity of the signal transduction mechanisms involved. The inhibitor studies described in this paper implicate a role for PKA in the regulation of the directional migratory response to applied electric fields, galvanotaxis.

Azepines↗

ET-1 inhibits B-16 murine melanoma cell migration by decreasing K(+) currents.

Cell migration is mediated by ion channels and transporters, and plays crucial roles in a variety of physiological and pathological processes. Previously, our studies have shown that a Ca(2+)-regulated K(+) current exists in B-16 murine melanoma cells, and that endothelin-1 (ET-1) inhibits the K(+) current via a PKC-dependent pathway. In the present study, patch-clamp whole-cell recording and transwell migration assays were used to examine the effects of ET-1 on B-16 murine melanoma cell migration. ET-1 (100 nM in the injection pipette and 10 nM in the incubation medium) decreased the K(+) current amplitude by 33.0 +/- 2.5% and inhibited migration of B-16 cells by 57.4 +/- 9.4%. Similarly, the Ca(2+)-regulated K(+) channel blockers, BaCl(2) and quinidine, decreased the K(+) current by 20.5 +/- 1.0% and 36.6 +/- 1.2%, respectively, and slowed migration of B-16 melanoma cells by 37.1 +/- 8.6% and 42.7 +/- 8.8%, respectively. The effect of ET-1 on the K(+) current and cell migration was simulated by ET-3. In contrast, the K(+) channel opener, diclofenac, increased the K(+) current by 128.8 +/- 11.7%, 257.4 +/- 35.8% at concentrations of 1 and 5 mM, respectively. Likewise, the migration of B-16 murine melanoma cells dramatically increased by 75.6 +/- 12.7% in the presence of 100 microM diclofenac in incubation medium. Furthermore, the ET-1- and ET-3-induced inhibition of K(+) current and migration was abrogated by diclofenac. In the presence of diclofenac, ET-1 only reduced the K(+) current amplitude by 10.6 +/- 1.1%, and slowed B-16 cell migration by only 10.8 +/- 8.9%. The results suggest that the K(+) channel-dependent migration of B-16 melanoma cells is modulated by ET-1. Cell Motil.

Animals↗

Timing and patterns of astrocyte migration from xenogeneic transplants of the cortex and corpus callosum.

The timing, pattern, and pathway of astrocyte migration were investigated in vivo by transplantation of CD-1 mouse cerebral cortex (E13-14) or corpus callosum (P2-3) into neonatal rat cortex. A monoclonal antibody specific for a mouse astrocyte surface antigen (M2) was used to identify the location of the grafts and the migrated donor astrocytes. Within the host cortex, astrocytes from cortical grafts began migration at post-transplantation day (PTD) 7. Over the next 4 days, the most distant displaced donor cells were found progressively further away from the grafts, migrating at a rate of about 220 microns/day. After PTD 11, the migration rate for the farthest displaced donor cells slowed to 25 microns/day, and the cells appeared to stop at about PTD 16 at a distance of 1,100 microns from the edge of the graft. Astrocytes had a faster migration speed in the white matter and covered a longer distance (5 mm) than those in the gray matter, extending on occasion into the contralateral hemisphere. The patterns of astrocyte migration differed depending on local cues around the transplant. Donor astrocytes that had been implanted into the host cortex migrated toward the host cortical surface, sometimes in several radial lines. Astrocytes from grafts, especially callosal grafts, placed in the subcortical white matter migrated along the host fiber tracts. Many astrocytes transplanted into the hippocampus formed laminar patterns close to the hippocampal neuronal layers. These results suggest that the direction, pattern, and speed of astrocyte migration are influenced by local substrates in the host brain.

Animals↗