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PubMed2005

A Rac switch regulates random versus directionally persistent cell migration.

Directional migration moves cells rapidly between points, whereas random migration allows cells to explore their local environments. We describe a Rac1 mechanism for determining whether cell patterns of migration are intrinsically random or directionally persistent. Rac activity promoted the formation of peripheral lamellae that mediated random migration. Decreasing Rac activity suppressed peripheral lamellae and switched the cell migration patterns of fibroblasts and epithelial cells from random to directionally persistent. In three-dimensional rather than traditional two-dimensional cell culture, cells had a lower level of Rac activity that was associated with rapid, directional migration. In contrast to the directed migration of chemotaxis, this intrinsic directional persistence of migration was not mediated by phosphatidylinositol 3'-kinase lipid signaling. Total Rac1 activity can therefore provide a regulatory switch between patterns of cell migration by a mechanism distinct from chemotaxis.

Cell Culture Techniques↗
PubMed1980

Mast cell heparin stimulates migration of capillary endothelial cells in vitro.

Migration of capillary endothelial cells is an important component of angiogenesis in vivo. Increased numbers of mast cells have been associated with several types of angiogenesis. We have used a quantitative assay in vitro to demonstrate that mast cells release a factor that significantly increases bovine capillary endothelial cell migration. The factor is present in medium conditioned by mast cells as well as lysates of mast cells. The stimulatory effect of mast cells on migration is specific for capillary endothelial cells. Furthermore, mast cells have no mitogenic activity for capillary endothelial cells. Of all the secretory products of mast cells tested, only heparin stimulated capillary endothelial cell migration in vitro. Heparin preparations from a variety of sources stimulated capillary endothelial cell migration to the same degree but did not stimulate migration of several other cell types. The migration activity of heparin and mast cell conditioned medium was blocked by specific antagonists of heparin (protamine and heparinase), but not by chondroitinase ABC. The migration activity of mast cell conditioned medium was resistant to heat (100 degrees C) and incubation with proteolytic enzymes. These results suggest that the role of mast cells in angiogenesis may be to enhance migration of the endothelial cells of growing capillaries.

Animals↗
PubMed1996

Rat blood neutrophils express very late antigen 4 and it mediates migration to arthritic joint and dermal inflammation.

Blood neutrophils contribute to joint injury in human and experimental models of arthritis. Neutrophil migration out of the blood in joint inflammation involves both the CD18 (beta2) integrins and a CD18 integrin-independent pathway. To investigate this migration, radiolabeled rat blood neutrophils were used to measure neutrophil accumulation in the inflamed joints of rats with adjuvant arthritis and the role of leukocyte integrins in migration to these joints and to dermal inflammation was determined. Neutrophils migrated rapidly (<2 h) to the inflamed joints 14-18 d after immunization with adjuvant. Blocking monoclonal antibodies (mAbs) to both LFA-1 and Mac-1 together, as well as a mAb to CD18, inhibited neutrophil accumulation in the inflamed joints by 50-75%. However, migration to dermal inflammation induced by C5a(des Arg)' tumor necrosis factor alpha, lipopolysaccharide, and poly-inosine:cytosine was inhibited by approximately 90%. Flow cytometry revealed the expression of low levels of very late antigen 4 (VLA-4) on nearly all rat blood neutrophils. Treatment with anti-VLA-4 plus anti-LFA-1 but neither mAb alone, strongly (60-75%) inhibited neutrophil accumulation in arthritic joints. This mAb combination also inhibited neutrophil migration to dermal inflammatory reactions by 30-70%. Blocking VLA-4 together with the CD18 integrins inhibited neutrophil accumulation by 95-99%, virtually abolishing neutrophil accumulation in cutaneous inflammation. A similar blockade of VLA-4 and CD18 decreased neutrophil accumulation in the inflamed joints by 70-83%, but a significant portion of the neutrophil accumulation to these joints still remained. In conclusion, rat blood neutrophils express functional VLA-4 that can mediate neutrophil migration to both inflamed joints and dermal inflammatory sites. VLA-4 appears to be able to substitute for LFA-1 in this migration and is particularly important for accumulation in inflamed joints. However, there exists an additional CD18- and VLA-4-independent pathway of neutrophil migration to arthritic joints that is not involved in acute dermal inflammation.

Animals↗
PubMed2004

R-Ras controls membrane protrusion and cell migration through the spatial regulation of Rac and Rho.

Although it is known that the spatial coordination of Rac and Rho activity is essential for cell migration, the molecular mechanisms regulating these GTPases during migration are unknown. We found that the expression of constitutively activated R-Ras (38V) blocked membrane protrusion and random migration. In contrast, expression of dominant negative R-Ras (41A) enhanced migrational persistence and membrane protrusion. Endogenous R-Ras is necessary for cell migration, as cells that were transfected with siRNA for R-Ras did not migrate. Expression of R-Ras (38V) decreased Rac activity and increased Rho activity around the entire cell periphery, whereas expression of dominant negative R-Ras (41A) showed the converse, suggesting that R-Ras can spatially activate Rho and inactivate Rac. Consistent with this role, endogenous R-Ras localized and was preferentially activated at the leading edge of migratory cells in response to adhesion. The effects of R-Ras on cell migration are mediated by PI3-Kinase, as an effector mutant that uncouples PI3-Kinase binding from R-Ras (38V) rescued migration. From these data, we hypothesize that R-Ras plays a key role in cell migration by locally regulating the switch from Rac to Rho activity after membrane protrusion and adhesion.

Cell Adhesion↗
PubMed2001

GABA(B) receptors mediate motility signals for migrating embryonic cortical cells.

During development, postmitotic neurons migrate from germinal regions into the cortical plate (cp), where lamination occurs. In rats, GABA is transiently expressed in the cp, near target destinations for migrating neurons. In vitro GABA stimulates neuronal motility, suggesting cp cells release GABA, which acts as a chemoattractant during corticogenesis. Pharmacological studies indicate GABA stimulates migration via GABA(B)-receptor (GABA(B)-R) activation. Using immunohistochemistry, RT-PCR and Western blotting, we examined embryonic cortical cell expression of GABA(B)-Rs in vivo. At E17, GABA(B)-R1(+) cells were identified in the ventricular zone (vz) and cp. RT-PCR and Western blotting demonstrated the presence of GABA(B)-R1a and GABA(B)-R1b mRNA and proteins. Using immuno- cytochemistry, GABA(B)-R expression was examined in vz and cp cell dissociates before and after migration to GABA in an in vitro chemotaxis assay. GABA-induced migration resulted in an increase of GABA(B)-R(+) cells in the migrated population. While <20% of each starting dissociate was GABA(B)-R(+), >70% of migrated cells were immunopositive. We used a microchemotaxis assay to analyze cp cell release of diffusible chemotropic factor(s). In vitro, cp dissociates induced vz cell migration in a cell density-dependent manner that was blocked by micromolar saclofen (a GABA(B)-R antagonist). HPLC demonstrated cp cells release micromolar levels of GABA and taurine in several hours. Micromolar levels of both molecules stimulated cell migration that was blocked by micromolar saclofen. Thus, migratory cortical cells express GABA(B)-Rs, cp cells release GABA and taurine, and both molecules stimulate cortical cell movement. Together these findings suggest GABA and/or taurine act as chemoattractants for neurons during rat cortical histogenesis via mechanisms involving GABA(B)-Rs.

Amino Acids↗
PubMed1994

Stimulation of migration of human aortic smooth muscle cells by vitronectin: implications for atherosclerosis.

OBJECTIVE: Migration of smooth muscle cells into the neointima has been implicated in atherogenesis. Vitronectin, a serum factor that promotes cell spreading and attachment, accumulates in atherosclerotic human tissues. The aim of this study was to determine the role of vitronectin and its receptor (integrin alpha V beta 3) in migration of smooth muscle cells. METHODS: Human aortic smooth muscle cell migration was studied in modified Boyden chambers. Expression of vitronectin receptor was determined by northern blotting of receptor mRNA and immunoprecipitation of receptor protein. RESULTS: Vitronectin dose dependently increased smooth muscle cell migration by an amount comparable to that induced by platelet derived growth factor, (PDGF)-BB. Antiserum to alpha V beta 3 diminished vitronectin driven migration. Northern blot analysis showed low constitutive expression of alpha V and beta 3 mRNA by smooth muscle cell and rapid induction with transforming growth factor beta (TGF-beta) and thrombin. Immunoprecipitation confirmed increased synthesis of the alpha V beta 3 vitronectin receptor complex by TGF-beta or thrombin. Smooth muscle cells pretreated with TGF-beta or thrombin showed increased vitronectin driven migration. cAMP suppressed induction of migration, but inhibition of protein kinase C increased it. CONCLUSIONS: These results show that vitronectin-induced human aortic smooth muscle cell migration is mediated by alpha V beta 3 vitronectin receptor and expression of the receptor is induced by TGF-beta and thrombin, which in turn induce vitronectin driven, vitronectin receptor modulated smooth muscle cell migration.

Arteriosclerosis↗
PubMed1992

Comparative effects of pollen and seed migration on the cytonuclear structure of plant populations. II. Paternal cytoplasmic inheritance.

We continue our study of the effects of pollen and seed migration on the cytonuclear structure of mixed-mating plant populations by analyzing two deterministic continent-island models under the critical assumption of paternal cytoplasmic inheritance. The major results of this study that contrast with our previous conclusions based on maternal cytoplasmic inheritance are (i) pollen gene flow can significantly affect the cytonuclear structure of the island population, and in particular can help to generate cytonuclear disequilibria that greatly exceed the magnitude of those that would be produced by seed migration or mixed mating alone; (ii) with simultaneous pollen and seed migration, nonzero cytonuclear disequilibria will be maintained not only when there is disequilibrium in the immigrant pollen or seeds, but also through a variety of intermigrant admixture effects when the two pools of immigrants differ appropriately in their cytonuclear compositions; (iii) either immigrant pollen or immigrant seeds can generate disequilibria de novo in populations with initially random cytonuclear associations, but pollen migration alone generally produces lower levels of disequilibrium than does comparable seed migration, especially at high levels of self-fertilization when the overall fraction of immigrant pollen is low; (iv) the equilibrium state of the island population will be influenced by the rate of pollen gene flow whenever there is either allelic disequilibrium in the immigrant pollen or simultaneous seed migration coupled with different cytoplasmic or nuclear allele frequencies in immigrant pollen and seeds or nonzero allelic disequilibrium in either immigrant pool. The estimation of pollen migration should therefore be facilitated with paternal cytoplasmic inheritance relative to the case of maternal cytoplasmic inheritance. These basic conclusions hold whether the population is censused as seeds or as adults, but with simultaneous pollen and seed migration, the relationship between census time and the ability to detect nonrandom cytonuclear associations is complex. When migration is through pollen alone, however, the cytonuclear structure of the island population is independent of the life stage censused.

Alleles↗
PubMed1999

stumps, a Drosophila gene required for fibroblast growth factor (FGF)-directed migrations of tracheal and mesodermal cells.

Fibroblast growth factors (FGFs) bind to FGF receptors, transmembrane tyrosine kinases that activate mitogenic, motogenic, and differentiative responses in different tissues. While there has been substantial progress in elucidating the Ras-MAP kinase pathway that mediates the differentiative responses, the signal transduction pathways that lead to directed cell migrations are not well defined. Here we describe a Drosophila gene called stumps that is required for FGF-dependent migrations of tracheal and mesodermal cells. These migrations are controlled by different FGF ligands and receptors, and they occur by different cellular mechanisms: the tracheal migrations occur as part of an epithelium whereas the mesodermal migrations are fibroblast-like. In the stumps mutant, tracheal cells fail to move out from the epithelial sacs, and only rudimentary tracheal branches form. Mesodermal cells fail in their dorsal migrations after gastrulation. The stumps mutation does not block all FGF signaling effects in these tissues: both random cell migrations and Ras-MAP kinase-mediated induction of FGF-specific effector genes occurred upon ectopic expression of the ligand or upon expression of a constitutively activated Ras protein in the migrating cells. The results suggest that stumps function promotes FGF-directed cell migrations, either by potentiating the FGF signaling process or by coupling the signal to the cellular machinery required for directed cell movement.

Animals↗
PubMed2005

IgE- and FcepsilonRI-mediated migration of human basophils.

Local accumulation of basophils at inflammatory sites is observed in experimental antigen challenge and in allergic diseases. It is not fully known what factor(s) regulates local basophil influx in tissues, and it has not been determined whether antigens belong in a panel of basophil chemoattractants. This study was designed to elucidate whether IgE- and high-affinity receptor for IgE (FcepsilonRI)-mediated stimulation can induce human basophil migration. The migration-inducing potency of an anti-FcepsilonRI alpha-chain mAb, CRA-1, was examined on human basophils. CRA-1 mAb elicited significant migration of basophils. The migration-inducing potency of this mAb was maximal at 100 ng ml-1, and CRA-1 mAb at 100 ng ml-1 attracted approximately 10% of total inoculated basophils above baseline levels after incubation for 2.5 h. Checkerboard analysis indicated that basophil migration induced by this mAb was mainly chemotactic and partially chemokinetic. An antigen, Der f 2, also induced migration of basophils from Der f-sensitive subjects. Basophils mixed with 1 ng ml-1 of CRA-1 mAb showed an exaggerated migration response to eotaxin, indicating that FcepsilonRI cross-linkage enhances basophil migration to other chemoattractants. Induction of basophil migration by IgE- and FcepsilonRI-cross-linking stimulation may, at least in part, explain the pathogenesis of local basophil accumulation clinically observed in allergic diseases such as asthma.

Antigens, Dermatophagoides↗
PubMed2004

Both mitogen-activated protein kinase and phosphatidylinositol 3-kinase signalling are required in epidermal growth factor-induced human trophoblast migration.

Adequate extravillous trophoblast (EVT) invasion is an essential step for placental formation. The aim of this study was to examine the possible role of phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signalling in epidermal growth factor (EGF)-induced EVT migration and to determine if the 70 kDa ribosomal S6 kinase (p70S6K) is involved in this process. In this study, EGF significantly stimulated HTR8/SVneo cell migration and the phosphorylation of AKT, ERK1/2 and p70S6K in a concentration-dependent manner. The MAPK inhibitor U0126 decreased cell migration and ERK phosphorylation, but it did not influence p70S6K phosphorylation in response to EGF. In the presence of PI3K inhibitors (Wortmannin), EGF-stimulated trophoblast migration and phosphorylation of AKT and P70S6K (Thr(389) and Thr(421)/Ser(424)) were decreased, while EGF-induced ERK phosphorylation was not affected. Expression of an activated AKT (Myr-AKT2) increased basal phospho-p70S6K (Thr(389) and Thr(421)/Ser(424)) content, but failed to stimulate cell migration. However, it induced cell migration in the presence of EGF and Wortmannin, in which both AKT and MAPK pathways were activated. In addition, there was a concentration-dependent inhibition of cell migration and p70S6K phosphorylation (Thr(389) and Thr(421)/Ser(424)) in the presence of Rapamycin, a specific inhibitor of the mammalian target of rapamycin (mTOR, a downstream of AKT). Taken together, our data suggest that EGF-induced trophoblast migration involves the coordinated regulation of both PI3K/AKT and MAPK signalling pathways. mTOR/p70S6K is important in PI3K- but not MAPK-mediated trophoblast migration in response to EGF.

Animals↗
PubMed2003

Nitric oxide induces polarization of actin in encephalitogenic T cells and inhibits their in vitro trans-endothelial migration in a p70S6 kinase-independent manner.

Nitric oxide (NO) inhibits both actively induced and transferred autoimmune encephalomyelitis. To explore potential mechanisms, we examined the ability of NO to inhibit migration of T lymphoblasts through both collagen matrices and monolayers of rat brain endothelial cells. The NO donor 1-hydroxy-2-oxo-3, 3-bis (2-aminoethyl)-1-triazene (HOBAT) inhibited migration in a concentration-dependent manner. NO pretreatment of T cells inhibited migration through untreated endothelial cells, but NO pretreatment of endothelial cells had no inhibitory effect on untreated T cells. Therefore NO's migration inhibitory action was mediated through its effect on T cells and not endothelial cells. HOBAT did not inhibit migration by inducing T-cell death but rather by polarizing the T cells, resulting in a morphology suggestive of migrating cells. P70S6 kinase, shown to have a role in NO-induced migration inhibition in fibroblasts, had no role in the inhibitory effect of NO on T-cell migration. Thus, HOBAT did not alter p70S6K activity nor did rapamycin, a specific inhibitor of p70S6K, inhibit HOBAT-induced T-cell morphological changes or T-cell migration. We suggest that NO-induced morphological changes result in T cells with predefined migratory directionality, thus limiting the ability of these cells to respond to other migratory signals.

Actin Cytoskeleton↗
PubMed2003

Potentiation by cyclic AMP of the stimulatory effect of epidermal growth factor on corneal epithelial migration.

PURPOSE: To provide insight into the mechanism by which epidermal growth factor (EGF) stimulates corneal epithelial migration, we investigated the possible interaction between EGF and cyclic AMP (cAMP) signaling pathways during epithelial migration with an organ culture system for the rabbit cornea. METHODS: Rabbit corneal blocks were cultured in the absence or presence of various agents for 24 hours and were then fixed, dehydrated, embedded in paraffin, sectioned, and stained with hematoxylin-eosin. The path length of epithelial migration was measured on light micrographs of the stained sections. RESULTS: Epidermal growth factor alone stimulated corneal epithelial migration in a dose-dependent manner. In contrast, neither of two cell-permeable cAMP analogs, dibutyryl cAMP and 8-bromo cAMP, affected epithelial migration at concentrations up to 1 mM. In the presence of EGF (10 ng/mL), however, each of the two cAMP derivatives increased the extent of epithelial migration in a concentration-dependent manner. Neither the adenylate cyclase activator forskolin nor the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine alone affected epithelial migration. However, each of these two agents potentiated the stimulatory effect of EGF on this process. The stimulatory effects of fibronectin, hyaluronan, and interleukin-6 on corneal epithelial migration were not modified by either dibutyryl cAMP or 3-isobutyl-1-methylxanthine. CONCLUSION: These results demonstrate that cAMP potentiates the stimulation of corneal epithelial migration by EGF in vitro, suggesting that endogenous cAMP might function as a modulator of epithelial wound healing promoted by this growth factor in vivo.

1-Methyl-3-isobutylxanthine↗
PubMed2003

Enteropathogenic Escherichia coli: stimulating neutrophil migration across a cultured intestinal epithelium without altering transepithelial conductance.

INTRODUCTION: Migration of neutrophils across the intestinal epithelium is the hallmark of inflammatory conditions of the bowel. In cultured intestinal epithelial monolayer models, neutrophils can be induced to migrate along a chemotactic gradient such as n-formyl-methionyl-leucyl-phenylalanine (fMLP). Physical passage of the neutrophils across the epithelium could disrupt the tight-junctions, possibly leading to a large increase in the transepithelial conductance (G(t)). The goal of this study is to determine whether transepithelial migration of neutrophils induced by enteropathogenic (EPEC) causes changes in G(t) comparable with those seen with fMLP. METHODS: The apical side of T84 monolayers were rapidly infected with EPEC E2348/69 or exposed to 1 microM fMLP. A third group of monolayers exposed to neither EPEC nor fMLP served as control. Indium-labeled neutrophils were added to the serosal side of monolayers grown on a cell culture insert membrane (12 microm pores). G(t) was measured at fixed intervals up to 4 hours. After a 150-minute incubation, radioactivity of the neutrophils that migrated to the apical side was assayed and the number of migrating neutrophils was calculated. RESULTS: At 150 minutes, EPEC induced similar neutrophil chemotactic capability compared to fMLP (231 +/- 34.10(3) and 193 +/- 48.10(3), respectively, n = 13, P > 0.05). However, EPEC-induced neutrophil migration was not associated with significant increase in G(t), 1.13 +/- 0.16 fold of baseline G(t), in distinction with fMLP groups, 13.3 +/- 0.48 fold, n = 7 (P< 0.05). G(t) changes with EPEC were seen after 4 hours of infection, but were not different in the presence or absence of neutrophil migration (1.37 +/- 0.12 fold and 1.42 +/- 0.17 fold of baseline G(t), respectively). CONCLUSIONS: The results indicate that EPEC-induced neutrophil migration can occur without significant disruption of barrier function. In addition, the chemo-attractant recruiting neutrophils during EPEC infection is unlikely to be fMLP; and, the G(t) increase seen with fMLP-driven recruitment may indicate a discretionary compromise of barrier function during neutrophil migration.

Bacterial Adhesion↗
PubMed1998

Effect of the endothelin family of peptides on human coronary artery smooth-muscle cell migration.

The migration of coronary artery medial smooth-muscle cells (SMCs) is one of the key events in the process of intimal thickening in coronary atherosclerotic lesions. The objectives of the present study were to determine whether any of the three isoforms of endothelin (ET), ET-1, ET-2, and ET-3, or an intermediate form of ET, big ET-1, induces migration of human coronary artery SMCs, and to investigate the possible interaction of ET peptides and well-known migration-stimulatory factors, platelet-derived growth factor (PDGF)-BB and angiotensin II (Ang II), on SMC migration by the Boyden's chamber method. None of the ET peptides alone induced SMC migration between 10(-9) and 10(-7) mol/L. In contrast, ET-1 and ET-2 significantly induced SMC migration in the presence of low concentrations of PDGF-BB (0.5 ng/mL) or Ang II (10(-9) mol/L), although ET-3 was less active (ET-1 = ET-2 > ET-3). In contrast, big ET-1 was without significant activity on PDGF-BB-or Ang II-induced SMC migration. The potentiation of SMC migration by ET peptides was clearly inhibited by the ETA receptor antagonist BG-123 in a concentration-dependent manner. These results suggest that the ET family of peptides, especially ET-1 and ET-2, can induce human coronary artery SMC migration in combination with PDGF-BB or Ang II, probably via ETA receptors. Taken together with the finding that the concentrations of ET, PDGF-BB and Ang II are locally increased at sites of endothelial injury, this indicates that ET may be an initial stimulus for human coronary artery medial SMC recruitment during coronary atherosclerosis, possibly in combination with PDGF-BB or Ang II.

Angiotensin II↗
PubMed2006

Proximal migration can be measured accurately on standardized anteroposterior shoulder radiographs.

UNLABELLED: During the last decade, investigators of several studies have stressed the importance of early diagnosis and treatment of rotator cuff tears to improve outcome of surgical repair. Proximal migration of the humeral head is thought to be indicative for rotator cuff disorders. We wanted to assess the accuracy of proximal migration measurement on anteroposterior radiographs. Computed tomography scans and anteroposterior radiographs of 43 shoulders in 26 patients were taken using the same protocol. Proximal migration was measured as the acromiohumeral interval and the upward migration index. The mean absolute difference for the upward migration index was only 0.06 (standard deviation, 0.07), this was less then 5% of the mean upward migration index measured on computed tomography reformations. The correlation coefficient and Bland-Altman plot showed a strong correlation between computed tomography and radiographic measurements, especially for the upward migration index (correlation coefficient, 0.82). Our results indicate that measurement of subacromial space on anteroposterior radiographs, controlled for positioning, scaling, and individual differences by using the upward migration index, presents an accurate measurement for proximal migration. LEVEL OF EVIDENCE: Diagnostic study, Level I (testing of previously developed diagnostic criteria on consecutive patients--with universally applied reference "gold" standard). See the Guidelines for Authors for a complete description of levels of evidence.

Aged↗
PubMed2003

Graft migration or displacement after multilevel cervical corpectomy and strut grafting.

STUDY DESIGN: A retrospective review of consecutive patients with graft migration or displacement after anterior cervical corpectomy surgery was performed. OBJECTIVES: To examine the associated risk factors and results of treatment among patients who sustained graft displacement or migration after anterior cervical corpectomy surgery. SUMMARY OF BACKGROUND DATA: Graft migration or displacement after anterior cervical corpectomy is a potential complication that may require revision surgery, but because of the low incidence, the factors associated with graft movement and the results of treatment are not well defined. METHODS: All patients who had undergone a cervical corpectomy were examined for graft migration or displacement. None of the patients had a previous cervical laminectomy or prior posterior cervical surgery. All the patients were treated with autogenous strut grafting after decompression. RESULTS: Over a 25-year period, 249 consecutive patients underwent one- to five-level anterior cervical corpectomies and strut grafting. All the patients were fused using autogenous bone grafts (iliac crest or fibula). During the postoperative period, 16 of the patients (10 women and 6 men; average age, 61.4 years) experienced migration of their grafts. The average follow-up period was 4.7 years (range, 2-12 years). The graft migration rates increased with more levels of fusion (odds ratio of 1.65 for having a displaced graft with each additional level): 4 of 95 single-level grafts, 4 of 76 two-level grafts, 7 of 71 three-level grafts, and 1 of 6 for four-level grafts. Of the 16 patients with graft migration, 14 had procedures involving a corpectomy of C6 with a fusion inferiorly extending to the C7 vertebral body (P = 0.001, statistically significant difference). Of these 16 patients, 5 underwent revision surgeries acutely for displacement and associated fracture of the inferior graft and vertebral body junction. None of the patients sustained a neurologic or respiratory complication as a result of graft migration ordisplacement. All of the patients went on to successfulfusion. CONCLUSIONS: This study demonstrated that a greater number of vertebral bodies removed and a longer graft are directly related to an increased frequency of graft displacement. Graft displacement may require revision surgery, but no patient in this study experienced a permanent adverse result from this complication. Corpectomies involving a fusion ending at the C7 vertebral body were associated with a higher rate of graft migration.

Adult↗
PubMed1993

Mouse dendritic epidermal T cells exhibit chemotactic migration toward PAM 212 keratinocyte culture supernatants.

Dendritic epidermal T cells (DETCs) are Thy-1+, CD45+, CD3+, CD4-, CD8-, and T-cell receptor-V gamma 3/V delta 1+ leukocytes that reside normally in adult mouse skin. We have demonstrated previously that keratinocytes serve as adhesion substrates for DETCs, and that interleukin 7 (IL-7), which is produced by keratinocytes, serves as a growth factor for DETCs. The present study was conducted to address the mechanisms by which DETCs migrate into the epidermis, reasoning that keratinocytes may also be a source of chemotactic activity. Short-term DETC lines were 35S-labeled and tested for migration toward Pam 212 keratinocyte culture supernatants using a modified Boyden chamber method; cell movement from upper chambers toward test samples in lower chambers was traced by counting radioactivity. DETC displayed rapid (within 60 min) and marked (> 50%) migration toward keratinocyte supernatants. The majority of cells that had migrated into keratinocyte supernatants expressed the V gamma 3 T-cell receptor, thus verifying that the migrating cells were DETCs. Addition of keratinocyte supernatants to the upper chambers completely blocked migration, suggesting its chemotactic nature. By contrast, no DETC migration was observed toward 3T3 fibroblast supernatants. Chemotactic activities were 1) produced by Pam 212 cells even in the absence of serum; 2) greater than 12 kD in size; 3) heat and pH labile; 4) trypsin sensitive; and 5) precipitated by 60-100% ammonium sulfate. Several cytokines (e.g., IL-1 alpha and IL-8) failed to mediate DETC migration when added to the lower chambers. Likewise, the same cytokines, when added to the upper chambers, failed to inhibit DETC migration toward Pam 212 supernatants. These results support our hypothesis that keratinocytes facilitate the residence of DETC in epidermis by secreting unique chemotactic factors, by providing adhesion substrates, and by elaborating specific growth factors.

Animals↗
PubMed2005

Neutrophil differentiated HL-60 cells model Mac-1 (CD11b/CD18)-independent neutrophil transepithelial migration.

During active intestinal inflammation granulocytes accumulate in the lumen of the gut where they damage the epithelium through the release of various products such as reactive oxygen species and proteolytic enzymes. Previously, using function blocking monoclonal antibodies, we showed that neutrophil migration across intestinal epithelial monolayers in response to various chemoattractants was partially beta(2) integrin Mac-1 (CD11b/CD18)-independent. Here, we show that treating neutrophils with intact monoclonal antibody (mAb) to CD18 activates the cells to express more CD11b. Thus our goal now was to determine whether neutrophil Mac-1-independent transepithelial migration proceeds independently of prior cell activation through Mac-1. We took two approaches, one using blocking Fab' fragments of mAb to CD18 and the second was to develop a neutrophil differentiated HL-60 cell line which is Mac-1 deficient to further study neutrophil/epithelial cell interaction. Anti-CD18 Fab' minimally activated neutrophils but inhibited approximately 75% of transepithelial migration to fMLP while having a minimal effect (</=25% inhibition) on the migration to C5a. Upon incubation with dimethylsulphoxide, HL-60 cells differentiated and up-regulated CD11b expression and migrated to C5a and n-formyl methionyl leucyl phenylalanine in a similar manner to peripheral blood neutrophils. In contrast, CD11b expression was minimal on HL-60 cells differentiated with dibutytyl cAMP to a neutrophil-like phenotype. These cells, however, readily migrated across both intestinal and lung epithelial monolayers in response to C5a. We conclude that Mac-1-independent transepithelial migration does not require prior activation of cells via Mac-1 ligation because HL-60 cells lacking Mac-1 (CD11b/CD18) expression migrate effectively. HL-60 cells differentiated with dbcAMP should greatly assist in the search for the Mac-1-independent ligands for neutrophil migration across epithelium.

Antibodies, Monoclonal↗