scholarly journals Dendritic cell expression of the transcription factor T-bet regulates mast cell progenitor homing to mucosal tissue

2007 ◽  
Vol 204 (2) ◽  
pp. 431-439 ◽  
Author(s):  
Pilar Alcaide ◽  
Tatiana G. Jones ◽  
Graham M. Lord ◽  
Laurie H. Glimcher ◽  
Jenny Hallgren ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mast Cell ◽  
Adhesion Molecule ◽  
Trichinella Spiralis ◽  
Cellular Adhesion ◽  
Cell Trafficking ◽  
Peripheral Tissues ◽  
Cellular Adhesion Molecule

The transcription factor T-bet was identified in CD4+ T cells, and it controls interferon γ production and T helper type 1 cell differentiation. T-bet is expressed in certain other leukocytes, and we recently showed (Lord, G.M., R.M. Rao, H. Choe, B.M. Sullivan, A.H. Lichtman, F.W. Luscinskas, and L.H. Glimcher. 2005. Blood. 106:3432–3439) that it regulates T cell trafficking. We examined whether T-bet influences homing of mast cell progenitors (MCp) to peripheral tissues. Surprisingly, we found that MCp homing to the lung or small intestine in T-bet−/− mice is reduced. This is reproduced in adhesion studies using bone marrow–derived MCs (BMMCs) from T-bet−/− mice, which showed diminished adhesion to mucosal addresin cellular adhesion molecule–1 (MAdCAM-1) and vascular cell adhesion molecule–1 (VCAM-1), endothelial ligands required for MCp intestinal homing. MCp, their precursors, and BMMCs do not express T-bet, suggesting that T-bet plays an indirect role in homing. However, adoptive transfer experiments revealed that T-bet expression by BM cells is required for MCp homing to the intestine. Furthermore, transfer of WT BM-derived dendritic cells (DCs) to T-bet−/− mice restores normal MCp intestinal homing in vivo and MCp adhesion to MAdCAM-1 and VCAM-1 in vitro. Nonetheless, T-bet−/− mice respond vigorously to intestinal infection with Trichinella spiralis, eliminating a role for T-bet in MC recruitment to sites of infection and their activation and function. Therefore, remarkably, T-bet expression by DCs indirectly controls MCp homing to mucosal tissues.

scholarly journals The Epithelial Cellular Adhesion Molecule (EP-Cam) Is a Ligand for the Leukocyte-Associated Immunoglobulin-like Receptor (Lair)

2001 ◽  
Vol 194 (1) ◽  
pp. 107-112 ◽  
Author(s):  
Linde Meyaard ◽  
Anne-Renée van der Vuurst de Vries ◽  
Talitha de Ruiter ◽  
Lewis L. Lanier ◽  
Joseph H. Phillips ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Immune Cell ◽  
Human Leukocyte ◽  
Cellular Adhesion ◽  
Epidermal Growth Factor Domain ◽  
Cell Functions ◽  
Cellular Adhesion Molecule ◽  
Human Intestinal Epithelium

Human leukocyte-associated immunoglobulin-like receptor (LAIR)-1 is expressed on many cells of the immune system and is predicted to mediate inhibitory functions based on the presence of immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in its cytoplasmic domain. Although the role of LAIR-1 in the regulation of immune responses in vivo is unknown, LAIR-1 cross-linking by monoclonal antibody inhibits various immune cell functions in vitro. Here, we identify the coloncarcinoma-associated epithelial cellular adhesion molecule (Ep-CAM) as a ligand for LAIR-1 and LAIR-2, a related soluble LAIR-1 family member. Ep-CAM interacts with the LAIR molecules through its first epidermal growth factor domain; Ep-CAM–specific antibodies can abrogate the binding. Intraepithelial T lymphocytes express LAIR-1 and thus may interact with Ep-CAM present on human intestinal epithelium. We propose that LAIR-1–Ep-CAM interaction may contribute to mucosal tolerance and that LAIR-2 possibly modulates this function.

scholarly journals Pax6-dependent regulation of adhesive patterning, R-cadherin expression and boundary formation in developing forebrain

Development ◽  
1997 ◽  
Vol 124 (19) ◽  
pp. 3765-3777 ◽  
Author(s):  
A. Stoykova ◽  
M. Gotz ◽  
P. Gruss ◽  
J. Price
Keyword(s):  
Transcription Factor ◽  
Cellular Adhesion ◽  
Cellular Mechanisms ◽  
Adhesive Properties ◽  
Vitro Assay ◽  
Boundary Formation ◽  
Developmental Abnormalities ◽  
Homophilic Adhesion

Mutations in the gene for the transcription factor, Pax6, induce marked developmental abnormalities in the CNS and the eye, but the cellular mechanisms that underlie the phenotype are unknown. We have examined the adhesive properties of cells from the developing forebrain in Small eye, the Pax6 mutant mouse. We have found that the segregation normally observed in aggregates of cortical and striatal cells in an in vitro assay is lost in Small eye. This correlates with an alteration of in vivo expression of the homophilic adhesion molecule, R-cadherin. Moreover, the boundary between cortical and striatal regions of the telencephalon is dramatically altered in Small eye: radial glial fascicles do not form at the border, and the normal expression of R-cadherin and tenascin-C at the border is lost. These data suggest a link between the transcription factor, Pax6, R-cadherin expression, cellular adhesion and boundary formation between developing forebrain regions.

In vivo exit of c-kit+/CD49dhi/β7+ mucosal mast cell precursors from the bone marrow following infection with the intestinal nematode Trichinella spiralis

Blood ◽  
2004 ◽  
Vol 103 (7) ◽  
pp. 2655-2660 ◽  
Author(s):  
Joanne L. Pennock ◽  
Richard K. Grencis
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Mast Cells ◽  
Trichinella Spiralis ◽  
Mucosal Mast Cell ◽  
Hematopoietic Tissue ◽  
In Vivo Experiments ◽  
Intestinal Nematode

Abstract We have used the parasite helminth Trichinella spiralis to study the generation and differentiation of mast cell progenitors in the bone marrow of mice, as this infection triggers an intestinal mastocytosis which correlates with parasite expulsion. C-kit+ mast cell progenitors have previously been defined by methylcellulose colony-forming units and by limiting dilution assays in vitro. In vivo experiments have demonstrated the essential requirement by mast cells for specific integrin expression. We have defined 2 c-kit+ populations in the bone marrow, one of which coexpresses CD49d/β7 integrin, a marker essential for small intestine immigration. We have confirmed the phenotype of these cells by using antagonistic anti-c-kit antibody in vivo. Our data show that the loss of c-kit+/β7+ cells from the bone marrow correlates with their appearance in the blood and precedes detection of mature mast cells in the gut by 3 days. This exit correlates with an increase in soluble stem cell factor (SCF) in the serum, suggesting that the c-kit/SCF interaction may be chemotactic or haptotactic in nature. This study shows that during infection the bone marrow environment generates mast cells destined for the intestinal mucosa before their exit into the periphery, indicating a clear interplay between infection site and hematopoietic tissue. (Blood. 2004;103:2655-2660)

scholarly journals Mononuclear phagocytes egress from an in vitro model of the vascular wall by migrating across endothelium in the basal to apical direction: role of intercellular adhesion molecule 1 and the CD11/CD18 integrins.

1996 ◽  
Vol 183 (2) ◽  
pp. 451-462 ◽  
Author(s):  
G J Randolph ◽  
M B Furie
Keyword(s):  
Adhesion Molecule ◽  
In Vitro Model ◽  
Umbilical Vein ◽  
Cellular Adhesion ◽  
Mononuclear Phagocytes ◽  
Apical Surface ◽  
Apical Direction ◽  
Cellular Adhesion Molecule ◽  
Vitro Model

Little is known about how mononuclear phagocytes (MP) are cleared from sites of inflammation as inflammatory lesions resolve. In this study, the possibility that MP could be cleared from tissues by migrating across endothelium in the basal to apical direction was investigated. In an in vitro model of a blood vessel wall consisting of human umbilical vein endothelial cells (HUVEC) grown on amniotic tissue, a majority of MP that initially transmigrated into the amnion later exited by migrating back across the endothelium in the basal to apical direction. MP that egressed from these cultures adhered to the apical surface of the endothelium or were found nonadherent in the medium above the endothelium. Egression of MP continued throughout the 4-d period examined, displaying higher than first order kinetics and a t(1/2) of approximately 24 h. These kinetics were decreased by increasing the volume of medium bathing the cultures, suggesting that a soluble factor(s) regulates the rate of egression. In contrast, the kinetics were accelerated by pretreating the endothelium with IL-1. The initial phase of this increased rate of egression was inhibited by antibodies to inter- cellular adhesion molecule 1 (ICAM-1) or CD18 by 100 and 71%, respectively. Immunostaining revealed that ICAM-1 was present on the apical and basal surfaces of umbilical vein endothelium in vitro and in situ. These data demonstrate that MP can traverse endothelium in the basal to apical direction, and lend insight into the mechanisms by which this process occurs.

Abstract 1047: Infusion of Reconstituted High Density Lipoproteins Into Humans Enhances the In Vitro Anti-Inflammatory Capacity of the High Density Lipoprotein Fraction.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Sanjay Patel ◽  
Brian Drew ◽  
Stephen Duffy ◽  
Shirley Nahkla ◽  
Kerry-Anne Rye ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Cellular Adhesion ◽  
High Density ◽  
High Density Lipoproteins ◽  
Human Coronary Artery ◽  
Cellular Adhesion Molecule ◽  
Anti Inflammatory

Background: Intravenous infusions of reconstituted high density lipoproteins (rHDL) have been shown to promote regression of coronary atheroma. Here we investigate the effects of rHDL infusion on the anti-inflammatory capacity of the isolated HDL fraction. Methods: Eight fasting Type 2 Diabetics (mean age 52 ± 2 years) received IV saline or apolipoprotein A-I (apoA-I)/phosphatidylcholine complexes (rHDL) at an apoA-I dose of 80mg/kg, on separate occasions in random order. The HDL fraction was isolated from subjects at baseline, 4 & 72hrs after infusion and assayed for chemical composition. The anti-inflammatory capacity of HDL preparations was assessed by incubation for 16hrs with human coronary artery endothelial cells. Cell expression of vascular cell adhesion molecule-1 (VCAM-1) and inter-cellular adhesion molecule (ICAM-1) 5 hrs after TNF-α stimulation was quantitated by flow cytometry. Results : Saline infusion had no effect on concentration or anti-inflammatory capacity of isolated HDL. rHDL infusion increased the concentration of HDL apoA-I (at baseline, 4h & 72h, [apoA-I] = 966 ± 105, 2562 ± 330 & 1701 ± 180 (ug/mL) respectively), as well as HDL cholesterol and HDL phospholipids. The addition of equivalent volumes of HDL (100uL) isolated at each time point inhibited VCAM-1 (Panel A) and ICAM-1 (Panel B) expression in proportion to the apoA-I concentration of the isolated HDL (p<0.01 ANOVA across time points for both VCAM-1/ICAM-1 expression and apoA-I concentration) (see figure ). Conclusions: Infusion of rHDL in humans increases the concentration of HDL apoA-I. The anti-inflammatory capacity of isolated HDL is enhanced in proportion to its apoA-I concentration.

scholarly journals Transcription factor Erg regulates angiogenesis and endothelial apoptosis through VE-cadherin

Blood ◽  
2008 ◽  
Vol 111 (7) ◽  
pp. 3498-3506 ◽  
Author(s):  
Graeme M. Birdsey ◽  
Nicola H. Dryden ◽  
Valerie Amsellem ◽  
Frank Gebhardt ◽  
Kapil Sahnan ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Transcription Factor ◽  
Adhesion Molecule ◽  
Umbilical Vein ◽  
Intercellular Junctions ◽  
Tube Formation ◽  
Endothelial Tube Formation ◽  
Umbilical Vein Endothelial Cells

Abstract Tight regulation of the balance between apoptosis and survival is essential in angiogenesis. The ETS transcription factor Erg is required for endothelial tube formation in vitro. Inhibition of Erg expression in human umbilical vein endothelial cells (HUVECs), using antisense oligonucleotides, resulted in detachment of cell-cell contacts and increased cell death. Inhibition of Erg expression by antisense in HUVECs also lowered expression of the adhesion molecule vascular endothelial (VE)–cadherin, a key regulator of endothelial intercellular junctions and survival. Using chromatin immunoprecipitation, we showed that Erg binds to the VE-cadherin promoter. Furthermore, Erg was found to enhance VE-cadherin promoter activity in a transactivation assay. Apoptosis induced by inhibition of Erg was partly rescued by overexpression of VE-cadherin–GFP, suggesting that VE-cadherin is involved in the Erg-dependent survival signals. To show the role of Erg in angiogenesis in vivo, we used siRNA against Erg in a Matrigel plug model. Erg inhibition resulted in a significant decrease in vascularization, with increase in caspase-positive endothelial cells (ECs). These results identify a new pathway regulating angiogenesis and endothelial survival, via the transcription factor Erg and the adhesion molecule VE-cadherin.

scholarly journals Constitutive homing of mast cell progenitors to the intestine depends on autologous expression of the chemokine receptor CXCR2

Blood ◽  
2005 ◽  
Vol 105 (11) ◽  
pp. 4308-4313 ◽  
Author(s):  
J. Pablo Abonia ◽  
K. Frank Austen ◽  
Barrett J. Rollins ◽  
Sunil K. Joshi ◽  
Richard A. Flavell ◽  
...  
Keyword(s):  
Mast Cell ◽  
Small Intestine ◽  
Adhesion Molecule ◽  
Chemokine Receptor ◽  
Cellular Adhesion ◽  
Wild Type ◽  
Cellular Adhesion Molecule ◽  
Mouse Small Intestine ◽  
Chemokine Receptor Cxcr2 ◽  
Cell Adhesion Molecule 1

Abstract Homing of mast cell progenitors (MCps) to the mouse small intestine involves the interaction of α4β7 integrin with mucosal addressin cellular adhesion molecule-1 (MAdCAM-1). We now demonstrate the dependence of this process on CXC chemokine receptor 2 (CXCR2) and vascular cell adhesion molecule-1 (VCAM-1) using null strains and mice sublethally irradiated and bone marrow (BM) reconstituted (SIBR) with wild-type or null BM or with wild-type BM followed by administration of blocking antibody. The intestinal MCp concentration in CXCR2-/- mice was reduced by 67%, but was unaltered in CC chemokine receptor 2-/- (CCR2-/-), CCR3-/-, or CCR5-/- mice. SIBR mice given CXCR2-/- BM had an intestinal MCp concentration that was 76% less than that in BALB/c BM reconstituted mice. Antibody blockade of VCAM-1 or of CXCR2 in SIBR mice reduced intestinal MCp reconstitution, and mice lacking endothelial VCAM-1 also had a marked reduction relative to wild-type mice. Finally, the half-life of intestinal MCps in wild-type mice was less than one week on the basis of a more than 50% reduction by administration of anti-α4β7 integrin or anti-CXCR2. Thus, the establishment and maintenance of MCps in the small intestine is a dynamic process that requires expression of the α4β7 integrin and the α-chemokine receptor CXCR2.

Anti-inflammatory effects of an inflammatory chemokine: CCL2 inhibits lymphocyte homing by modulation of CCL21-triggered integrin-mediated adhesions

Blood ◽  
2008 ◽  
Vol 112 (13) ◽  
pp. 5016-5025 ◽  
Author(s):  
Liat Flaishon ◽  
Gili Hart ◽  
Einat Zelman ◽  
Christine Moussion ◽  
Valentin Grabovsky ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Cell Trafficking ◽  
Lymphocyte Homing ◽  
Peripheral Tissues ◽  
Human T Cells ◽  
Peripheral Lymph ◽  
Anti Inflammatory ◽  
Fine Tune

Abstract Our studies focus on the pathways that restrict homing of specific subsets of immune cells, and thereby fine-tune the immune response at specific lymphoid and peripheral tissues. Here, we report that CCL2 (at picomolar [pM] levels) renders both murine and human T cells defective in their ability to develop CCR7-triggered activation of LFA-1– and LFA-1–mediated adhesion strengthening to endothelial ICAM-1 both in vitro and in vivo. CCL2 also attenuated lymphocyte chemotaxis toward lymph node chemokines. Consequently, low-dose CCL2 inhibited lymphocyte homing to peripheral lymph nodes but did not affect lymphocyte trafficking through the spleen. Impaired homing of lymphocytes to peripheral lymph nodes resulted in attenuated progression of both asthma and adjuvant arthritis. Thus, pM levels of circulating CCL2 can exert global suppressive effects on T-cell trafficking and differentiation within peripheral lymph nodes, and may be clinically beneficial as an anti-inflammatory agent.

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