Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “transmigration”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed1999

Impairment of HIV polymorphonuclear leukocyte transmigration across T84 cell monolayers: an alternative mechanisms for increased intestinal bacterial infections in AIDS?

Our objective was to study the influence of HIV infection of polymorphonuclear leukocytes (PMN) on transepithelial migration. To date, reports of functional PMN chemotaxis in AIDS are contradictory. This is the first attempt to assess this function via an in vitro model allowing transmigration of neutrophils through an intestinal epithelial barrier. PMN were isolated from 45 HIV-infected patients and 45 healthy volunteers. PMN transmigration across T84 epithelial cells was initiated by applying either various concentrations of formyl-met-leu-phe peptide (f-MLP) or interleukin-8 and assayed by quantification of myeloperoxidase activity. CD11b, CD18, and CD47 expression on PMN was compared before and after transepithelial migration by flow cytometry analysis. CD11b expression was studied by electron microscopy. Apoptosis of transmigrated HIV PMN and control PMN was investigated by morphology and DNA fragmentation characterization. Compared to control PMN, HIV PMN exhibited a decrease in transepithelial migration that directly correlated with CD4+ counts. Basal and transepithelial migration-mediated expression of CD11b, CD18, and CD47 were unmodified in HIV PMN compared to control PMN. Electron microscopy labeling confirmed no difference in CD11b expression on HIV and control PMN. The index of apoptosis in transmigrated HIV PMN and control PMN was identical. These data provide evidence of a defect in the f-MLP-induced chemotaxis of PMN from HIV-infected patients across an intestinal epithelial barrier. This defective migration is not due to a quantitative modification of CD11b, CD18 and CD47 on HIV PMN suggesting a more subtle alteration. The impairment in the transmigration function may contribute in vivo to an increased susceptibility to intestinal bacterial infection in HIV-infected patients.

Adult↗
PubMed1999

The immune system and the effects of non-volatile anesthetics on neutrophil transmigration through endothelial cell monolayers.

Inflammation represents the consequence of capillary dilation with accumulation of fluid and transmigration of leukocytes into the surrounding tissue. Leukocytes play a major role in the defense system of the body against invading microorganisms. This defense system has a non-specific branch consisting of granulocytes and macrophages and a specific branch of lymphocytes. Granulocytes release cytotoxic compounds from their intracellular granules into their local environment when encountering microorganisms. This random destruction happens rapidly, but it may also harm healthy tissue of the body. Leukocytes patrol the body by circulating through the blood and lymphatic system ensuring a continuous surveillance which is a prerequisite for an efficient defense. Upon tissue damage and inflammation, leukocytes are recruited from the blood to sites of injury, and this trafficking displays exquisite specificity. In the late 1890 s, Metchnikoff noted the power of certain blood cells to move towards microorganisms and ingest them. In fact, leukocytes adhere to the endothelium of the blood vessels, and subsequently leave the circulation by transmigration through the intercellular junctions of the endothelial cell monolayer. Transmigration is driven by chemoattractants, a process known as diapedesis. Reversible adherence of leukocytes to the endothelium, basement membranes, and other surfaces is an essential event in the establishment of inflammation, whose molecular basis is beginning to be understood. Inflammation may become chronic in many pathophysiologic processes and disease states. In long-term mechanically ventilated critically ill patients, non-volatile anesthetics are needed over a prolonged time period. Perioperative infections are a major cause of morbidity and mortality in critically ill patients. Therefore, the influence of non-volatile anesthetics and opioid agents on the immune system is of high interest. After presentation of the different effectors of the immune system and their fluxes through the body, the aim of this review is to propose a general model of leukocyte transmigration through endothelial cell monolayers. It emphasizes in which way different non-volatile anesthetic drugs may affect the non-specific branch of the immune system, i.e. the leukocyte transmigration through endothelial cell monolayers.

Anesthetics↗
PubMed2001

Eotaxin promotes eosinophil transmigration via the activation of the plasminogen-plasmin system.

The effect of eotaxin, a potent eosinophil chemotactic factor, on eosinophil transmigration through a reconstituted basal membrane (Matrigel) was evaluated. Eotaxin induced significant eosinophil transmigration in the presence of 10% fetal bovine serum (FBS) and interleukin-5. Its effect was optimal at 0.01 microM, and it plateaued at 18 h. Eotaxin's effect was greater with eosinophils from asthmatic subjects (61.1 +/- 3.4%) than with eosinophils from normal subjects (38.7 +/- 4.2%) (P < 0.001). Inhibition of metalloproteinases decreased eotaxin-induced transmigration by < or = 10.4%, whereas inhibition of the plasminogen-plasmin system decreased eotaxin's effect by < or = 44.4% (P = 0.0002). Moreover, eotaxin-induced transmigration was largely diminished in medium with low concentrations of serum [0.5% FBS: 6.1 +/- 2.4%; 10% FBS: 40.2 +/- 5.8% (P = 0.0001)] but returned to its initial level with the addition of plasminogen (2 U/mL) to 0.5% FBS (43.1 +/- 6.5%). These data show that eotaxin is an efficient promoter of eosinophil transmigration in vitro, that it is more potent with cells from asthmatics than with normal cells, and that its effect depends predominantly on the activation of the plasminogen-plasmin system.

Adult↗
PubMed1997

Heightened transmigrating activity of CD4-positive T cells through reconstituted basement membrane in patients with human T-lymphotropic virus type I-associated myelopathy.

We investigated the transmigrating activity of peripheral blood T cells of patients with human T-lymphotropic virus type I-associated myelopathy (HAM) through reconstituted basement membrane. The transmigrating activity of CD4+ T cells of HAM patients was increased significantly in comparison to that of anti-HTLV-I-seropositive carriers and HTLV-I-seronegative controls. However, the migrating activity of CD8+ T cells was not significantly different in HAM patients and controls. The activity of aminopeptidase-N in peripheral blood T cells of HAM patients also was increased significantly, as compared to that of controls. In addition, HTLV-I proviral load in transmigrating CD4+ T cells of HAM patients was increased significantly (two- to eight-fold), compared to that in nontransmigrating CD4+ cells. By contrast, no significant difference in HTLV-I proviral load was found between transmigrating and nontransmigrating CD4+ cells of HTLV-I-seropositive carriers, although copy numbers of HTLV-I proviral load were very low in them. The heightened transmigrating activity of CD4+ cells from HAM patients through reconstituted basement membrane is based on the increased activity of aminopeptidase-N. Collectively, these findings suggest that HTLV-I-infected CD4+ T cells play an important role in the early stage of the pathogenesis of HAM.

Adult↗
PubMed1998

Transmigration of CD34+ cells across specialized and nonspecialized endothelium requires prior activation by growth factors and is mediated by PECAM-1 (CD31).

The transmigration of hematopoietic progenitor cells (HPCs) across vascular endothelium is a critical step in the homing of transplanted stem cells, but the molecular basis for this is unknown. We used mobilized peripheral blood CD34(+) selected cells and cultured bone marrow microvascular (BMECs) and human umbilical vein endothelial cells (HUVECs) to investigate the adhesion and transendothelial migration of HPCs. Colony-forming cells (CFCs) in freshly isolated CD34(+) cells showed high levels of adhesion to both forms of endothelium (28% +/- 4% and 38% +/- 6% of granulocyte-macrophage colony-forming cells [GM-CFCs] adhering to HUVECs and BMECs, respectively), but were unable to migrate to any significant extent across either (1.0% +/- 0.3% and 1.1% +/- 0.6% of GM-CFCs migrating across HUVECs and BMECs, respectively). Greater than 95% of peripheral blood CD34(+) cells are in G0/G1 of the cell cycle, but after 48 to 72 hours of stimulation with growth factors (interleukin-3 [IL-3] 12 ng/mL, stem cell factor 10 ng/mL, and IL-6 10 ng/mL), 28% +/- 5% of cells were in S+G2/M. Growth factor stimulation had no effect on the adhesion of mobilized CFCs but resulted in enhanced migration of these cells (9.8% +/- 1.6% and 12. 6% +/- 3.1% of GM-CFCs migrating across HUVECs and BMECs, respectively; P < .01, n = 6). Assessment of cell proliferation by the 3H-thymidine suicide method showed that, whereas 11.7% +/- 3.3% of proliferating CFCs transmigrated across endothelium, only 1.3% +/- 0.3% of nonproliferating CFCs did so (P < .05, n = 5). Transmigration of growth factor-activated CFCs was inhibited by anti-CD18 monoclonal antibody (MoAb; 50% +/- 18% inhibition) and by anti-platelet endothelial cell adhesion molecule-1 (PECAM-1) MoAb (70.8% +/- 7.1% inhibition; P < .05, n = 3). IL-1 stimulation of HUVECs had no significant effect on CD34(+) cell transmigration, but caused marked enhancement of neutrophil migration. Stem cell homing may depend, in part, on the ability of local cytokines to upregulate the transmigratory ability of these cells. The transmigration of HPCs shares at least some molecular pathways with that of mature cells (CD18 and PECAM-1), but is differently affected by endothelial activation.

Antigens, CD34↗
PubMed1992

ICAM-1-independent lymphocyte transmigration across high endothelium: differential up-regulation by interferon gamma, tumor necrosis factor-alpha and interleukin 1 beta.

The adhesion of lymphocytes to cytokine-treated high endothelium was studied using cultured high endothelial cells (HEC). Pretreatment of the HEC layer with a variety of cytokines caused up-regulation of lymphocyte adhesion with the effects ordered interferon gamma (IFN-gamma) greater than tumor necrosis factor-alpha (TNF-alpha) greater than or equal to interleukin 1 beta (IL 1 beta). Increased lymphocyte adhesion was found to be independent of ICAM-1 as expression by HEC was not increased by cytokines and antibodies against ICAM-1 did not block adhesion. The peptide CS1 and anti-beta 1 integrin subunit antibodies, however, caused partial inhibition of lymphocyte adhesion thus indicating a role for fibronectin on HEC and alpha 4 beta 1 on lymphocytes. Study of the kinetics of lymphocyte adhesion showed that the effects of IFN-gamma and TNF-alpha were persistent and remained detectable 2.5 h after removal of the cytokines whereas the effects of IL 1 beta were transient and were not sustained beyond 1 h. All of the cytokines used caused transient increases in the number of surface-bound lymphocytes with IFN-gamma greater than TNF-alpha greater than or equal to IL 1 beta, however, the most dramatic effect was on the transmigration of lymphocytes across the HEC. Both IFN-gamma and TNF-alpha caused sustained increased transmigration with IFN-gamma having the greater effect. IL 1 beta had little effect on transmigration. This model demonstrates that the binding and transmigration of lymphocytes across HEC can be differentially regulated by the actions of individual cytokines. These results support the concept that locally produced cytokines regulate HEC function within the lymph node.

Animals↗
PubMed1999

Migration of leukocytes across endothelium and beyond: molecules involved in the transmigration and fate of monocytes.

Passage of leukocytes across the endothelial lining into sites of inflammation has been shown to be regulated largely by platelet/endothelial cell adhesion molecule-1 (PECAM/CD31). We summarize recent work from our laboratory documenting that PECAM is involved both in diapedesis and the subsequent step of migration across the basal lamina. The former process involves a homophilic interaction between the amino-terminal extracellular domains of PECAM on the leukocyte and on the endothelial cell. The latter process involves a heterophilic interaction between the membrane-proximal extracellular domain of PECAM and an unknown ligand(s) in the subendothelial basal lamina. These findings are demonstrated in both in vitro and in vivo models. For monocytes, however, transmigration is just the first step in the next phase of their lives. In addition to their specific recruitment during the inflammatory response, many monocytes constitutively leave the bloodstream to enter tissues. However, only a fraction of these become tissue macrophages. In an in vitro model of monocyte emigration, approximately half of the leukocytes that initially transmigrate an endothelial monolayer migrate back out in the basal-to-apical direction within the next 2 days. This reverse transmigration cannot be blocked by anti-PECAM reagents, but involves p-glycoprotein and tissue factor expressed on the leukocytes. The reverse transmigrating cells are phenotypically dendritic cells (DC). Their maturation to mature DC can be accelerated by inclusion of inflammatory stimuli in the co-culture. The cells that remain behind in the subendothelial collagen are phenotypically macrophages. We postulate that a major source of DC in lymph nodes is cells derived from monocytes that enter a tissue via the blood and leave several days later via afferent lymphatic channels.

Animals↗
PubMed2004

Use of ICAM-1 antibodies and antisense oligonucleotides to inhibit transmigration of neutrophils.

OBJECTIVE: The increase in adhesion molecule expression during the initial phase of inflammation leads to transmigration of neutrophils. Inhibition of this transmigration could decrease inflammatory response and tissue damage. MATERIALS AND METHODS: Uptake of fluorescein-labelled oligonucleotides, expression of ICAM-1 and neutrophil migration were studied using the bilayer of epithelial (H292) and endothelial (ECV-304) cell lines and neutrophils from peripheral blood of healthy volunteers. RESULTS: The inhibition of ICAM-1 expression was time dependent for both cell lines, with inhibition of more than 50% after 48 h. Antisense oligos inhibited transmigration already after 4 h of incubation (6.6 +/- 2.5% versus 18.6 +/- 2.5% inhibition, p < 0.01). Antisense was more effective in preventing fMLP-induced neutrophil migration than ICAM-1 antibodies (88 +/- 3.8% versus 67 +/- 7% inhibition, p = 0.02). CONCLUSIONS: Antisense oligos cause a decrease in ICAM-1 expression and inhibit transmigration of neutrophils. However the effectiveness of antisense is higher than monoclonal antibodies, neither of them is able to block the migration completely. This suggests the existence of ICAM-1 independent mechanisms that are responsible for migration.

Antibodies↗
PubMed2002

Vascular immunotargeting of glucose oxidase to the endothelial antigens induces distinct forms of oxidant acute lung injury: targeting to thrombomodulin, but not to PECAM-1, causes pulmonary thrombosis and neutrophil transmigration.

Oxidative endothelial stress, leukocyte transmigration, and pulmonary thrombosis are important pathological factors in acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Vascular immunotargeting of the H(2)O(2)-generating enzyme glucose oxidase (GOX) to the pulmonary endothelium causes an acute oxidative lung injury in mice.(1) In the present study we compared the pulmonary thrombosis and leukocyte transmigration caused by GOX targeting to the endothelial antigens platelet-endothelial cell adhesion molecule (PECAM) and thrombomodulin (TM). Both anti-PECAM and anti-TM delivered similar amounts of (125)I-GOX to the lungs and caused a dose-dependent, tissue-selective lung injury manifested within 2 to 4 hours by high lethality, vascular congestion, polymorphonuclear neutrophil (PMN) sequestration in the pulmonary vasculature, severe pulmonary edema, and tissue oxidation, yet at an equal dose, anti-TM/GOX inflicted more severe lung injury than anti-PECAM/GOX. Moreover, anti-TM/GOX-induced injury was accompanied by PMN transmigration in the alveolar space, whereas anti-PECAM/GOX-induced injury was accompanied by PMN degranulation within vascular lumen without PMN transmigration, likely because of PECAM blockage. Anti-TM/GOX caused markedly more severe pulmonary thrombosis than anti-PECAM/GOX, likely because of TM inhibition. These results indicate that blocking of specific endothelial antigens by GOX immunotargeting modulates important pathological features of the lung injury initiated by local generation of H(2)O(2) and that this approach provides specific and robust models of diverse variants of human ALI/ARDS in mice. In particular, anti-TM/GOX causes lung injury combining oxidative, prothrombotic, and inflammatory components characteristic of the complex pathological picture seen in human ALI/ARDS.

Animals↗
PubMed1999

A standardized, a computer-assisted in vitro assay for the assessment of neutrophil transmigration across endothelial monolayers.

We describe an automated, observer-independent and highly reproducible assay for the quantification of transmigrated neutrophils across endothelial monolayers. Endothelial cells grown on collagen gels were loaded with a dye emitting red fluorescence. Neutrophils loaded with dye emitting green fluorescence were allowed to adhere to and transmigrate across endothelial monolayers. For quantification of adherent and migrated cells, randomly selected fields were scanned by confocal laser scan microscopy at defined depths within and below the endothelial monolayers. The images obtained were transferred into the public domain NIH image program and numbers and distribution of cells within scanned sectors were automatically calculated. We demonstrate that adherent neutrophils are easily discriminated from transmigrated cells; absolute numbers of migrated cells can be reproducibly calculated by counting cells at a depth of -20 microm, thus permitting evaluation of large-scale experiments: the efficacy of neutrophil transmigration depends on the level of endothelial activation after TNF stimulation and mAbs to cell surface adhesion molecules interfere with migration in a manner similar to that previously shown in in vivo experiments. This assay lends itself to the identification of molecules influencing in cell migration in each phase of EC activation and to the screening of pro- and anti-migratory properties of biological or pharmacological reagents.

Animals↗
PubMed1999

Mediator-dependent effects of pentoxifylline on endothelium for transmigration of neutrophils.

In the present study, we investigated the effects of the anti-inflammatory drug pentoxifylline (PTX) on activation of endothelial cells for enhanced adhesion and transmigration of neutrophils by lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF), interleukin-1 (IL-1) and granulocyte colony-stimulating factor (G-CSF). To evaluate the mechanism by which PTX exerts its effect, human umbilical vein endothelial cells (HUVEC) were pretreated with theophylline, 2'-O-dibutyryl-3', 5'-cyclic adenosine monophosphate (db cAMP), and 3-isobutyl-1-methylxanthine, respectively, prior to stimulation. Pretreatment of HUVEC with PTX significantly antagonized TNF-, IL-1-, and G-CSF-activated transmigration of neutrophils. Additive stimulatory effects of PTX were seen with LPS. With the exception of theophylline, all other test cAMP-raising agents stimulated transmigration in similar fashion to PTX. Upon stimulation with TNF or LPS, HUVEC produced IL-8 and PTX affected this process in opposing fashions, with inhibition of the effects of TNF and augmentation of those of LPS. These results demonstrate that PTX differentially affects mediator-induced activation of HUVEC. The present IL-8 dependent and cAMP-regulated augmentation of LPS-induced stimulation of transmigration is the first description of an additive effect of PTX with a pro-inflammatory agent.

1-Methyl-3-isobutylxanthine↗
PubMed2000

The impact of eotaxin- and IL-5-induced adhesion and transmigration on eosinophil activity markers.

Eosinophils accumulate at sites of allergic inflammation, and play important roles in asthma/allergic disorders. The mechanism of eosinophil recruitment into tissues is not fully understood. In this study, we evaluated whether adhesion and/or transmigration, in the presence of IL-5 and eotaxin, alter the expression of CD9, CD11b, the beta1alpha4-integrin, and the EG2-epitope on intracellular ECP. We also investigated whether CD9 is involved in the adhesion process. With flow cytometry the surface expression of CD9, CD11b and the beta1alpha4-integrin, and the intracellular expression of EG2, were analyzed before, and after transmigration/adhesion to fibronectin. To evaluate the eventual role of CD9 in adhesion, eosinophils were preincubated with monoclonal antibodies to CD9. We observed decreased expression of CD9, and increased expression of CD11b on eosinophils, after adhesion and transmigration. The transmigration did not change the expression of the beta1alpha4-integrin or EG2, whereas the adhesion resulted in a decreased EG2 expression. Antibodies to CD9 decreased the adhesion property of eosinophils. The eosinophils are activated after both adhesion and transmigration by means of decreased CD9 and increased CD11b expression. The expression of the EG2-epitope on intracellular ECP was decreased when eosinophils adhered to fibronectin, probably due to degranulation. Our results also indicate that CD9 is involved in the adhesion of eosinophils to fibronectin.

Adolescent↗
PubMed2001

Transmigrant mandibular canines: a record of 28 cases and a retrospective review of the literature.

The transmigrant mandibular canine is a rare phenomenon. Most authors have described singular cases of unilateral or bilateral occurrence; however, a few authors have published more cases. This paper describes 28 cases exhibiting transmigratory canines. The observations are compared with observations from 39 earlier reports. Women are affected more than men. The left canine undergoes transmigration more commonly than does the right canine. Transmigration and impaction appear to be more common. Most of the patients do not have any symptoms, and these canines are often discovered at the radiological examination before orthodontic treatment. The etiology is obscure; however, abnormal displacement of the tooth bud in embryonic life is a commonly accepted explanation. Prolonged retention of the deciduous canine is a good clinical sign for a thorough radiological examination, preferably including an orthopantomographic radiograph. This would help in preventive measures. However, once established, a transmigrated canine requires surgical extraction. If possible, and if space is available and the patient is willing, all orthodontic efforts should be made to restore the normal position of this functionally very useful tooth in the human dentition.

Adolescent↗
PubMed2003

Tumor necrosis factor-alpha stimulates fractalkine production by mesangial cells and regulates monocyte transmigration: down-regulation by cAMP.

BACKGROUND: Fractalkine is a CX3C chemokine for mononuclear cells that has been implicated in the recruitment and accumulation of monocytes seen in glomerular diseases. We investigated the mechanisms by which tumor necrosis factor (TNF)-alpha stimulates mesangial cell (MC) fractalkine expression, and the effects of MC-derived fractalkine on monocyte transmigration. METHODS: Cultured rat MCs were incubated with TNF-alpha, with or without pretreatment with pharmacologic inhibitors of protein kinases or transcriptional factors downstream to TNF-alpha. Fractalkine mRNA and protein were analyzed by Northern and Western blotting. Translocation of nuclear factor (NF)-kappaB was evaluated by immunocytochemical staining. Monocyte transmigration was determined by in vitro chemotaxis assay. RESULTS: TNF-alpha stimulated MC fractalkine mRNA as well as cell-bound and soluble protein expression in a dose- and time-dependent manner. The soluble fractalkine was shed from the cell-bound form via metalloproteinase-dependent cleavage, and mediated in part TNF-alpha-induced monocyte transmigration in vitro. The incubation of MCs with calphostin C [a selective inhibitor of protein kinase C (PKC)] or PD98059 [a selective inhibitor of p42/44 mitogen-activated protein kinase (MAPK) kinase] attenuated TNF-alpha-stimulated fractalkine mRNA and protein expression. Coincubation of MCs with calphostin C and PD98059 resulted in a synergistic inhibition of TNF-alpha-stimulated fractalkine mRNA and protein expression. Incubation of MCs with phorbol myristate acetate (PMA) for four hours resulted in an increase in fractalkine mRNA expression that could be suppressed by calphostin C or depletion of PKC by pretreatment with PMA for 24 hours. Further, activation of PKC-depleted MCs with TNF-alpha stimulated fractalkine mRNA expression that could be blocked by calphostin C. PD 98059, but not calphostin C, inhibited TNF-alpha-activated phospho-p42/44 MAPK and phospho-c-Jun levels, whereas only calphostin C inhibited TNF-alpha-activated phosphorylation of PKCzeta/iota. The incubation of MCs with MG132, a NF-kappaB inhibitor, abolished TNF-alpha-induced degradation of inhibitory protein of NF-kappaB (I-kappaB)alpha, nuclear translocation of NF-kappaB, and fractalkine expression, without affecting phospho-c-Jun levels. In contrast, curcumin, an activating protein (AP)-1 inhibitor, attenuated TNF-alpha-stimulated phospho-c-Jun levels and fractalkine expression without discernible effects on TNF-alpha-induced degradation of I-kappaBalpha or NF-kappaB nuclear translocation. Neither PD 98059 nor calphostin C affected TNF-alpha-induced degradation of I-kappaBalpha or NF-kappaB nuclear translocation. Additional experiments examining the role of cAMP on MC fractalkine expression showed that the incubation of MCs with TNF-alpha and either db-cAMP or forskolin attenuated TNF-alpha-stimulated fractalkine mRNA and protein expression, preceded by attenuation of TNF-alpha-activated phosphorylation of p42/44 MAPK, and c-Jun, but not phosphorylation of PKCzeta/iota or nuclear translocation of NF-kappaB. CONCLUSION: The present data indicate that TNF-alpha activation of PKCzeta/iota, p42/44 MAPK, c-Jun/AP-1, and p65/NF-kappaB are involved in TNF-alpha-stimulated MC fractalkine expression, with the soluble fractalkine mediating in part the TNF-alpha-induced monocyte transmigration in vitro. Uncoupling of p42/44 MAPK or c-Jun/AP-1 signals may contribute to cAMP inhibition of MC fractalkine expression activated by TNF-alpha.

Animals↗
PubMedDate not supplied

In vitro infection of aortic endothelial cells by caprine arthritis encephalitis virus enhances in vitro transmigration of peripheral blood leukocytes and modulates their phenotypic expression.

Infection of goats by caprine arthritis-encephalitis virus (CAEV) provides a convenient example of the infiltration of various tissues by leukocytes following a natural lentiviral infection. This event is important in determining organ susceptibility and local immunity. Caprine vascular endothelial cells are susceptible to infection by CAEV in vitro, so we have investigated the consequences of this infection on the transmigration of uninfected leukocytes in an in vitro model. After in vitro infection by CAEV or stimulation by TNFalpha, the endothelial cells allowed the passage of tenfold more leukocytes from uninfected donors than did the uninfected endothelial cells. The transmigrating leukocytes were enriched in CD8+ lymphocytes, and the leukocytes appeared to have been activated during transmigration, as demonstrated by their expression of IL2R, MHC class II antigens and gamma-delta T-lymphocyte markers. CD4+, CD8+ and B-lymphocytes all proliferated in culture after transmigration. These results suggest that any possible infection or specific stimulation of endothelia in an infected animal could profoundly influence the choice of target organs and could activate the cells involved in local mucosal immune responses.

Animals↗
PubMed2003

Identification of proteases involved in the proteolysis of vascular endothelium cadherin during neutrophil transmigration.

Transmigration of neutrophils across the endothelium occurs at the cell-cell junctions where the vascular endothelium cadherin (VE cadherin) is expressed. This adhesive receptor was previously demonstrated to be involved in the maintenance of endothelium integrity. We propose that neutrophil transmigration across the vascular endothelium goes in parallel with cleavage of VE cadherin by elastase and cathepsin G present on the surface of neutrophils. This hypothesis is supported by the following lines of evidence. 1) Proteolytic fragments of VE cadherin are released into the culture medium upon adhesion of neutrophils to endothelial cell monolayers; 2) conditioned culture medium, obtained after neutrophil adhesion to endothelial monolayers, cleaves the recombinantly expressed VE cadherin extracellular domain; 3) these cleavages are inhibited by inhibitors of elastase; 4) VE cadherin fragments produced by conditioned culture medium or by exogenously added elastase are identical as shown by N-terminal sequencing and mass spectrometry analysis; 5) both elastase- and cathepsin G-specific VE cadherin cleavage patterns are produced upon incubation with tumor necrosis factor alpha-stimulated and fixed neutrophils; 6) transendothelial permeability increases in vitro upon addition of either elastase or cathepsin G; and 7) neutrophil transmigration is reduced in vitro in the presence of elastase and cathepsin G inhibitors. Our results suggest that cleavage of VE cadherin by neutrophil surface-bound proteases induces formation of gaps through which neutrophils transmigrate.

Animals↗
PubMed2000

Neutrophil-induced transmigration of tumour cells treated with tumour-conditioned medium is facilitated by granulocyte-macrophage colony-stimulating factor.

OBJECTIVE: To investigate the effect of different cytokines that are present in tumour-conditioned medium on human neutrophil (PMN)-induced tumour cell transmigration. DESIGN: Laboratory study. SETTING: University hospital, Ireland. MATERIAL: Isolated human PMN and cultured human breast tumour cell line, MDA-MB-231. INTERVENTIONS: Human PMN treated with either tumour-conditioned medium or different media neutralised with monoclonal antibodies (MoAb), and MDA-MB-231 cells were plated on macrovascular and microvascular endothelial monolayers in collagen-coated transwells to assess migration of tumour cells. MAIN OUTCOME MEASURES: Cytokines present in tumour-conditioned medium, PMN cytocidal function and receptor expression, and tumour cell transmigration. RESULTS: tumour-conditioned medium contained high concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), and interleukin 8 (IL-8), but not granulocyte colony-stimulating factor (G-CSF) and interleukin 3 (IL-3). Anti-GM-CSF MoAb significantly reduced PMN-induced transmigration of tumour cells treated with tumour-conditioned medium (p < 0.05), whereas anti-VEGF and anti-IL-8 MoAbs did not affect their migration. In addition, anti-GM-CSF MoAb, but not anti-VEGF or anti-IL-8 MoAb, reduced PMN CD11b and CD18 overexpression induced by tumour-conditioned medium (p < 0.05). CONCLUSION: These results indicate that the GM-CSF that is present in tumour-conditioned medium may be involved, at least in part, in alterations in PMN function mediated by the medium and subsequently PMN-induced transmigration of tumour cells.

Breast Neoplasms↗
PubMed2006

An inflammation-induced mechanism for leukocyte transmigration across lymphatic vessel endothelium.

The exit of antigen-presenting cells and lymphocytes from inflamed skin to afferent lymph is vital for the initiation and maintenance of dermal immune responses. How such an exit is achieved and how cells transmigrate the distinct endothelium of lymphatic vessels are unknown. We show that inflammatory cytokines trigger activation of dermal lymphatic endothelial cells (LECs), leading to expression of the key leukocyte adhesion receptors intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin, as well as a discrete panel of chemokines and other potential regulators of leukocyte transmigration. Furthermore, we show that both ICAM-1 and VCAM-1 are induced in the dermal lymphatic vessels of mice exposed to skin contact hypersensitivity where they mediate lymph node trafficking of dendritic cells (DCs) via afferent lymphatics. Lastly, we show that tumor necrosis factor alpha stimulates both DC adhesion and transmigration of dermal LEC monolayers in vitro and that the process is efficiently inhibited by ICAM-1 and VCAM-1 adhesion-blocking monoclonal antibodies. These results reveal a CAM-mediated mechanism for recruiting leukocytes to the lymph nodes in inflammation and highlight the process of lymphatic transmigration as a potential new target for antiinflammatory therapy.

Adult↗