Adhesion Of Polymorphonuclear Leukocytes Research Articles

Non-typeable Haemophilus influenzae directly and through TNF-α production enhances polymorphonuclear leukocytes adherence to bronchial epithelial cells and activation

Non-typeable Haemophilus influenzae directly and through TNF-α production enhances polymorphonuclear leukocytes adherence to bronchial epithelial cells and activation

Bacteria and Viruses in Periodontics- A review

Periodontal diseases are infectious diseases, but the specific mechanism by which the tooth-supportive tissue is destroyed is not clearly understood. Periodontitis is a multifactorial, chronic disease followed by destruction of encompassing structures of teeth and when left untreated leads to loss of alveolar bone and exfoliation of the involved teeth. The main etiological factor for development of periodontitis is oral biofilm containing anaerobic microorganisms. Microbiological culture studies have identified more than 1200 bacterial species in the oral cavity. Although the role of bacterial plaque in general seems to be evident, on the contrary the role of virus has been largely unexplored. Viral infection impairs periodontal defenses, thereby permitting subgingival overgrowth of periodontopathic bacteria. The role of viruses is significant, as they may induce abnormalities in the adhesion, chemotaxis, phagocytosis, and bactericidal activities of polymorphonuclear leukocytes. When associated with one another, viruses and bacteria have stronger periodonto-pathogenic potential than individually. Therefore, it is significant to know all etiologic factors and such an insight would lead to the better treatment of the disease.

Kidney vascular congestion exacerbates acute kidney injury in mice

Heart failure is frequently accompanied by kidney failure and co-incidence of these organ failures worsens the mortality in patients with heart failure. Recent clinical observations revealed that increased kidney venous pressure, rather than decreased cardiac output, causes the deterioration of kidney function in patients with heart failure. However, the underlying pathophysiology is unknown. Here, we found that decreased blood flow velocity in peritubular capillaries by kidney congestion and upregulation of endothelial nuclear factor-κB (NF-κB) signaling synergistically exacerbate kidney injury. We generated a novel mouse model with unilateral kidney congestion by constriction of the inferior vena cava between kidney veins. Intravital imaging highlighted the notable dilatation of peritubular capillaries and decreased kidney blood flow velocity in the congestive kidney. Damage after ischemia reperfusion injury was exacerbated in the congestive kidney and accumulation of polymorphonuclear leukocytes within peritubular capillaries was noted at the acute phase after injury. Similar results were obtained invitro, in which polymorphonuclear leukocytes adhesion on activated endothelial cells was decreased in flow velocity-dependent manner but cancelled by inhibition of NF-κB signaling. Pharmacological inhibition of NF-κB for the mice subjected by both kidney congestion and ischemia reperfusion injury ameliorated the accumulation of polymorphonuclear leukocytes and subsequent exacerbation of kidney injury. Thus, our study demonstrates the importance of decreased blood flow velocity accompanying activated NF-κB signaling in aggravation of kidney injury. Hence, inhibition of NF-κB signaling may be a therapeutic candidate for the vicious cycle between heart and kidney failure with increased kidney venous pressure.

Testosterone administration increases leukocyte-endothelium interactions and inflammation in transgender men

To evaluate the effect of testosterone treatment on metabolic and inflammation parameters and leukocyte-endothelium interactions in transgender men (TGM). Prospective observational study. University hospital. One hundred fifty-seven TGM. Administration of testosterone undecanoate (1,000 mg, intramuscular) every 12 weeks. Endocrine parameters, adhesion molecules (vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, and E-selectin), proinflammatory cytokines interleukin-6, and tumor necrosis factor alpha were evaluated in serum before and after treatment using Luminex's xMAP technology. In addition, interactions between human umbilical vein endothelial cells and polymorphonuclear leukocytes were assessed by flow chamber microscopy. Testosterone treatment led to an increase in leukocyte-endothelium interactions due to an increase in polymorphonuclear leukocytes rolling and adhesion and decreased rolling velocity. It also boosted levels of vascular cell adhesion molecule-1, E-selectin, interleukin-6, and tumor necrosis factor alpha. As expected, testosterone also produced a significant increase in free androgenic index, androstenedione, total testosterone, and atherogenic index of plasma and a decrease in sex hormone-binding globulin and high-density lipoprotein cholesterol. Treatment of TGM with testosterone induces an increase in leukocyte-endothelium interactions and adhesion molecules and proinflammatory cytokines. These effects are a reason to monitor cardiovascular risk in these patients.

Methionine and choline supply during the peripartal period alter polymorphonuclear leukocyte immune response and immunometabolic gene expression in Holstein cows

Polymorphonuclear leukocytes (PMNL) are the first responders upon pathogen invasion and hence play an important role in inflammatory and immune responses. Rumen-protected methionine (MET) and choline (CHOL) during the peripartal period affect the immune response and inflammatory status in dairy cows to different extents. We aimed to examine the effect of MET and CHOL supply on expression of genes regulating key PMNL functions and associations with whole-blood immune challenge. Thirty multiparous Holstein cows from a larger cohort randomly assigned from -21 to 30 d relative to parturition to a basal control (CON) diet, CON plus MET at a rate of 0.08% of dry matter, or CON plus CHOL at 60 g/d were used. Blood was sampled at -10, 7, and 30 d relative to parturition for inflammatory biomarker analyses and PMNL isolation. Neutrophil and monocyte phagocytosis and oxidative burst in vitro were assessed in whole blood at 1, 7, and 28 d. Although neutrophil and monocyte phagocytosis did not differ, oxidative burst in neutrophils and monocytes was greater in MET-supplemented cows relative to CON cows. Compared with CON, PMNL adhesion and migration-related genes (ITGAM, ITGB2, ITGA4) were downregulated in response to MET and CHOL. Expression of CADM1 and SELL was also lower in MET-supplemented cows compared with CON cows but not in CHOL cows. In contrast, compared with CON cows, the expression of ICAM1 was lower in CHOL but not MET cows. Similar to adhesion and migration-related genes, cows receiving MET- or CHOL-supplemented diets had lower expression of inflammation-related genes (IL1β, IL10RA, NFKB1, STAT3, TLR2). However, expression of IRAK1 and TLR4 was lower in MET- but not CHOL-supplemented cows. Plasma taurine concentration was greater in MET cows compared with CHOL and CON cows, suggesting a better redox status in plasma. In agreement with plasma taurine, oxidative stress-related genes (CBS, CTH, GPX1, GSS, SOD2) in PMNL were lower in response to MET and to CHOL supply. Overall, immunometabolic gene expression profile and blood biomarker analyses suggest an overall better redox status in PMNL during the transition period in response to MET and CHOL supply. These adaptations in PMNL might be beneficial for mounting a better bactericidal response upon challenge.

Effect of Temperature on the Morphometrical and Physical Parameters of Erythrocytes and Polymorphonuclear Leucocytes in Carassius gibelio (Bloch)

Dynamics of the morphometric and physical properties of hemocytes of the Prussian carp Carassius gibelio (Bloch) under the influence of a temperature factor has been studied with atomic force microscopy in experiments in vitro. It is found that, at a low incubation temperature (5°C), as opposed to room temperature (20°C), morphometric parameters change in erythrocytes; at a high temperature (40°C) they change in polymorphonuclear leucocytes. The low incubation temperature reduces the adhesion and elasticity of polymorphonuclear leucocytes and erythrocytes of C. gibelio, whereas a high incubation temperature leads to a decrease in adhesion in polymorphonuclear white blood cells.

Estrogen-dependent efficacy of limb ischemic preconditioning in female rats.

Our aim was to examine the effects of ischemic preconditioning (IPC) on the local periosteal and systemic inflammatory consequences of hindlimb ischemia-reperfusion (IR) in Sprague-Dawley rats with chronic estrogen deficiency (13 weeks after ovariectomy, OVX) in the presence and absence of chronic 17beta-estradiol supplementation (E2, 20 µg kg-1 , 5 days/week for 5 weeks); sham-operated (non-OVX) animals served as controls. As assessed by intravital fluorescence microscopy, rolling and the firm adhesion of polymorphonuclear neutrophil leukocytes (PMNs) gave similar results in the Sham + IR and OVX + IR groups in the tibial periosteal microcirculation during the 3-h reperfusion period after a 60-min tourniquet ischemia. Postischemic increases in periosteal PMN adhesion and PMN-derived adhesion molecule CD11b expressions, however, were significantly reduced by IPC (two cycles of 10'/10') in Sham animals, but not in OVX animals; neither plasma free radical levels (as measured by chemiluminescence), nor TNF-alpha release was affected by IPC. E2 supplementation in OVX animals restored the IPC-related microcirculatory integrity and PMN-derived CD11b levels, and TNF-alpha and free radical levels were reduced by IPC only with E2. An enhanced estrogen receptor beta expression could also be demonstrated after E2 in the periosteum. Overall, the beneficial periosteal microcirculatory effects of limb IPC are lost in chronic estrogen deficiency, but they can be restored by E2 supplementation. This suggests that the presence of endogenous estrogen is a necessary facilitating factor of the anti-inflammatory protection provided by limb IPC in females. The IPC-independent effects of E2 on inflammatory reactions should also be taken into account in this model. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:97-105, 2018.

Role of periodontopathogenic virus in periodontal disease: a review

Periodontal diseases are infectious diseases, but the specific mechanism by which the tooth-supportive tissue is destroyed is not clearly understood. Viral infection impairs periodontal defenses, thereby permitting subgingival overgrowth of periodontopathic bacteria. The role of viruses is significant, as they may induce abnormalities in the adhesion, chemotaxis, phagocytosis, and bactericidal activities of polymorphonuclear leukocytes. When associated with one another, viruses and bacteria have stronger periodontopathogenic potential than individually. Therefore, it is significant to know all etiologic factors and such an insight would lead to the better treatment of the disease.

Mutations of Cystic Fibrosis Transmembrane Conductance Regulator Gene Cause a Monocyte-Selective Adhesion Deficiency.

Cystic fibrosis (CF) is a common genetic disease caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Persistent lung inflammation, characterized by increasing polymorphonuclear leukocyte recruitment, is a major cause of the decline in respiratory function in patients with CF and is a leading cause of morbidity and mortality. CFTR is expressed in various cell types, including leukocytes, but its involvement in the regulation of leukocyte recruitment is unknown. We evaluated whether CF leukocytes might present with alterations in cell adhesion and migration, a key process governing innate and acquired immune responses. We used ex vivo adhesion and chemotaxis assays, flow cytometry, immunofluorescence, and GTPase activity assays in this study. We found that chemoattractant-induced activation of β1 and β2 integrins and of chemotaxis is defective in mononuclear cells isolated from patients with CF. In contrast, polymorphonuclear leukocyte adhesion and chemotaxis were normal. The functionality of β1 and β2 integrins was restored by treatment of CF monocytes with the CFTR-correcting drugs VRT325 and VX809. Moreover, treatment of healthy monocytes with the CFTR inhibitor CFTR(inh)-172 blocked integrin activation by chemoattractants. In a murine model of lung inflammation, we found that integrin-independent migration of CF monocytes into the lung parenchyma was normal, whereas, in contrast, integrin-dependent transmigration into the alveolar space was impaired. Finally, signal transduction analysis showed that, in CF monocytes, chemoattractant-triggered activation of RhoA and CDC42 Rho small GTPases (controlling integrin activation and chemotaxis, respectively) was strongly deficient. Altogether, these data highlight the critical regulatory role of CFTR in integrin activation by chemoattractants in monocytes and identify CF as a new, cell type-selective leukocyte adhesion deficiency disease, providing new insights into CF pathogenesis.

β2 integrins (CD11/18) are essential for the chemosensory adhesion and migration of polymorphonuclear leukocytes on bacterial cellulose.

Bacterial cellulose (BC) has been studied widely for applications in biomedical materials such as prosthetic artificial blood vessels owing to its unique characteristics, which include nontoxicity and nonimmunogenicity as compared with synthetic biopolymers such as expanded polytetrafluorethylene (ePTFE). However, to date, studies on the relative effect of leukocytes on BC as a prosthetic vascular graft are insufficient. Polymorphonuclear leukocytes (PMN) play a pivotal role in early-phase immune response to bacterial or periprosthetic infection. PMN recruitment at sites of infection or inflammation mediated by various integrins such as β2 integrin family (CD11/CD18 family). Therefore, we discuss our investigations into the mechanisms by which β2 integrins-mediated chemosensory adhesion and migration of PMN on the vascular graft surface, BC. Our results show that CD11b/CD18 components mainly mediate PMN adherence on BC. CD11b/CD18 displays weak coordination with the other two α subunits (CD11a and CD11c). Furthermore, it was found that the β subunit (CD18) plays a critical role in both the adhesion and migration of N-formylmethionyl-leucyl-phenylalanine (fMLP)-stimulated PMN on BC. The activity of CD18 contrasts with that of the individual α subunits. Among these, only CD11b displayed inhibition of PMN migration on BC surfaces.

Recruitment of inflammatory cells to the bladder endothelium exposed to cigarette smoke extract (669.1)

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a debilitating disease of unknown etiology. Several risk factors are associated with IC/PBS including smoking, weight and diet. Platelet activating factor (PAF) plays a role in inflammatory cell recruitment to the endothelium and we have shown that PAF metabolism by PAF‐acetylhydrolase (PAF‐AH) is inhibited by cigarette smoke. We propose that cigarette smoking inhibits bladder endothelial PAF‐AH activity and contributes directly to inflammatory cell recruitment in the bladder wall. Incubation of human bladder microvascular endothelial cells (HBMEC) with cigarette smoke extract (CSE, 20 µg/mL) resulted in a significant inhibition of PAF‐AH activity with increased PAF accumulation and polymorphonuclear leukocyte (PMN) adherence. Pretreatment of HBMEC with (S)‐bromoenol lactone to inhibit calcium‐independent phospholipase A2β and PAF production prior to CSE incubation lead to a significant reduction in PMN adherence to the bladder endothelium. Similarly, pretreatment of PMN with PAF receptor antagonists (WEB 4086 or Ginkgo biloba) prior to CSE caused a significant reduction in PMN adherence. We propose that targeting endothelial cell PAF production or blocking the PAF receptor may represent novel therapies for management of IC/PBS patients, particularly smokers.Grant Funding Source: Supported by a President's Research Fund, Saint Louis University grant

CXCL1/CXCL8 (GROα/IL-8) in human diabetic ketoacidosis plasma facilitates leukocyte recruitment to cerebrovascular endothelium in vitro

Diabetic ketoacidosis (DKA) in children is associated with intracranial vascular complications, possibly due to leukocyte-endothelial interactions. Our aim was to determine whether DKA-induced inflammation promoted leukocyte adhesion to activated human cerebrovascular endothelium. Plasma was obtained from children with type 1 diabetes either in acute DKA or in an insulin-controlled state (CON). Plasma concentrations of 21 inflammatory analytes were compared between groups. DKA was associated with altered circulating levels of ↑CXCL1 (GROα), ↑CXCL8 (IL-8), ↑IL-6, ↑IFNα2, and ↓CXCL10 (IP-10) compared with CON. These plasma analyte measurements were then used to create physiologically relevant cytokine mixtures (CM). Human cerebral microvascular endothelial cells (hCMEC/D3) were stimulated with either plasma (DKA-P or CON-P) or CM (DKA-CM or CON-CM) and assessed for polymorphonuclear leukocyte (PMN) adhesion. Stimulation of hCMEC/D3 with DKA-P or DKA-CM increased PMN adhesion to hCMEC/D3 under "flow" conditions. PMN adhesion to hCMEC/D3 was suppressed with neutralizing antibodies to CXCL1/CXCL8 or their hCMEC/D3 receptors CXCR1/CXCR2. DKA-P, but not DKA-CM, initiated oxidative stress in hCMEC/D3. Expression of ICAM-1, VCAM-1, and E-selectin were unaltered on hCMEC/D3 by either DKA-P or DKA-CM. In summary, DKA elicits inflammation in children associated with changes in circulating cytokines/chemokines. Increased CXCL1/CXCL8 instigated PMN adhesion to hCMEC/D3, possibly contributing to DKA-associated intracranial vascular complications.

Paeoniflorin suppresses vascular damage and the expression of E‐selectin and ICAM‐1 in a mouse model of cutaneous Arthus reaction

Paeoniflorin (PF) extracted from the root of Paeonia lactiflora pall, displays anti-inflammation properties in several animal models. Adhesion molecules are important for the recruitment of leucocyte to the vessel wall and involved in the pathogenesis of various autoimmune and inflammatory diseases. Herein, we investigate the effects of PF on adhesion molecule expression in a mouse model of cutaneous Arthus reaction and cultured human dermal microvascular endothelial cells (HDMECs). We showed that PF significantly ameliorated the immune complex (IC) induced vascular damage, leucocyte infiltrates and adhesion molecules expression. Furthermore, PF markedly blocked tumor necrosis factor-α (TNF-α)-induced E-selectin and intercellular adhesion molecule-1 (ICAM-1) expression in HDMECs at both mRNA and protein levels. PF also suppressed TNF-α-induced adhesion of polymorphonuclear leucocytes (PMNs) to HDMECs. Finally, western blot data revealed that PF can inhibit the phosphorylation of p38, JNK in TNF-α-treated HDMECs. These data suggest that PF, as an anti-inflammatory agent, can downregulate adhesion molecules expression. PF may be a candidate medicine for the treatment of IC-induced inflammatory response.

Carbon monoxide (CO)‐dependent modulation of polymorphonuclear leukocyte (PMN) adhesion to human cerebrovascular endothelial cells in an in vitro model of endotoxemia

CO liberated from a water‐soluble CO‐releasing molecule (CORM‐3) suppresses sepsis‐induced inflammation. However, the exact mechanisms are poorly understood.In this study we examined the mechanisms of CORM‐3‐dependent modulation of PMN adhesion in an in vitro model of endotoxemia employing human‐derived cerebrovascular endothelial cells, hCMEC/D3 (provided by Dr. P. Couraud, INSERM, Paris). hCMEC/D3 were stimulated with LPS (1μg/mL) for 6 hrs. In some experiments hCMEC/D3 were: 1) pre‐treated, 2) co‐treated, or 3) treated with CORM‐3 or inactive CORM‐3 (iCORM‐3) (200μM) before/during/following stimulation with LPS, respectively.PMN rolling/adhesion to hCMEC/D3 was assessed under conditions of flow (shear stress 0.7dyn/cm2). In parallel, MAPK‐signaling (phosphorylation of p38, ERK1/2 and JNK1/2; Western Blot) and expression of adhesion molecules (E‐selectin, ICAM‐1 and VCAM‐1; RT‐PCR) were also assessed.CORM‐3 significantly reduced PMN adhesion to hCMEC/D3 with the most profound effects seen in “pre‐treatment” group. This was accompanied by decreased levels of JNK1/2 Tyr‐phosphorylation and suppressed expression of E‐selectin and VCAM‐1.The results indicate that CORM‐3 interferes with activation of JNK1/2 phosphorylation and expression of hCMEC/D3 pro‐adhesive phenotype, thus potentially could be used to reduce systemic inflammation (HSFO‐393, HSFO‐NA6914, IRF‐04–79)

Sepsis-Associated Encephalopathy: Review of the Neuropsychiatric Manifestations and Cognitive Outcome

Sepsis-Associated Encephalopathy: Review of the Neuropsychiatric Manifestations and Cognitive Outcome

Human viruses and periodontal disease

Periodontitis is a multifactorial, chronic disease followed by destruction of supporting structures of teeth. The main etiological factor for development of periodontitis is oral biofilm containing anaerobic microorganisms. Besides bacteria, viruses can also be present within periodontal pockets. The role of viruses is significant, as they may induce abnormalities in the adhesion, chemotaxis, phagocytosis, and bactericidal activities of polymorphonuclear leukocytes. Associated with one another, viruses and bacteria have stronger periodontopathogenic potential than individually. The synergism between periodontopathogenic bacteria, Epstein-Barr virus, and Cytomegalovirus stands out. For full understanding of the pathogenesis of periodontitis, it is significant to know all etiologic factors and host immune response; such an understanding should also guide the adequate treatment of this disease.

Role of fine needle aspiration cytology in diagnosis of filarial infestation

Filariasis is a tropical disease transmitted by the Culex mosquitoes. The diagnosis of it is conventionally made by demonstrating microfilariae in the peripheral blood smear. However; microfilariae and adult filarial worm have been incidentally detected in fine needle aspirates of various lesions in clinically unsuspected cases. The cases of filariasis diagnosed by fine needle aspiration cytology (FNAC) were retrieved from the archives of the Cytopathology laboratory between the periods of January 1998 to February 2009. Both Papanicolaou- and May-Grunwald-Giemsa-stained smears were available in all the cases. A total of 26 diagnosed cases of filariasis were found, of which 19 were related to funiculo-epididymitis, four presented with breast lump, and three cases with lymphadenopathy. Smears revealed fragments of adult worm in 12 cases including 10 gravid female worm containing eggs and microfilariae and two male adult worm; whereas in remaining 14 cases only microfilariae or eggs were seen. Unfertilized eggs were seen in three cases and fertilized eggs were seen in five cases. Tissue response in the form of eosinophils in 16 cases, acute inflammatory exudate in five cases, macrophages in 22 cases, epitheloid cell granulomas in five cases, giant cells in four cases, lymphocytes in 10 cases, and plasma cells in three cases were seen. Adherence of polymorphonuclear leukocytes, eosinophils, and epithelioid cells were observed in four cases. On conclusion, filaria may affect the epididymis, spermatic cord, breast, and lymph node, and the accurate diagnosis can be easily and conveniently achieved by FNAC without any requirement of biopsy.

Design and characterization of a cleavage-resistant Annexin A1 mutant to control inflammation in the microvasculature

AbstractHuman polymorphonuclear leukocytes adhesion to endothelial cells during the early stage of inflammation leads to cell surface externalization of Annexin A1 (AnxA1), an effector of endogenous anti-inflammation. The antiadhesive properties of AnxA1 become operative to finely tune polymorphonuclear leukocytes transmigration to the site of inflammation. Membrane bound proteinase 3 (PR3) plays a key role in this microenvironment by cleaving the N terminus bioactive domain of AnxA1. In the present study, we generated a PR3-resistant human recombinant AnxA1—named superAnxA1 (SAnxA1)—and tested its in vitro and in vivo properties in comparison to the parental protein. SAnxA1 bound and activated formyl peptide receptor 2 in a similar way as the parental protein, while showing a resistance to cleavage by recombinant PR3. SAnxA1 retained anti-inflammatory activities in the murine inflamed microcirculation (leukocyte adhesion being the readout) and in skin trafficking model. When longer-lasting models of inflammation were applied, SAnxA1 displayed stronger anti-inflammatory effect over time compared with the parental protein. Together these results indicate that AnxA1 cleavage is an important process during neutrophilic inflammation and that controlling the balance between AnxA1/PR3 activities might represent a promising avenue for the discovery of novel therapeutic approaches.

E0047 Alphalinonenic acid inhibits high glucosemediated endothelial neutrophil adhesion by decreasing adhesion molecule expression via PI3KAkt pathway

ObjectiveNeutrophil-endothelial adhesion is crucial to vascular injury, the major cause of diabetic vascular complications. We studied the mechanism of cardio-protective effect of Alpha-linolenic acid (ALA).MethodsHuman umbilical vein endothelial cells (HUVECs)...

Thymus cell antigen 1 (Thy1, CD90) is expressed by lymphatic vessels and mediates cell adhesion to lymphatic endothelium

The lymphatic vascular system plays an important role in inflammation and cancer progression, although the molecular mechanisms involved are poorly understood. As determined by comparative transcriptional profiling studies of ex vivo isolated mouse intestinal lymphatic endothelial cells versus blood vascular endothelial cells, thymus cell antigen 1 (Thy1, CD90) was expressed at much higher levels in lymphatic endothelial cells than in blood vascular endothelial cells. These findings were confirmed by quantitative PCR, and at the protein level by FACS and immunofluorescence analyses. Thy1 was also strongly expressed by tumor-associated lymphatic vessels, as evaluated in a B16 melanoma footpad model in mice. Blockade of Thy1 inhibited tumor cell adhesion to cultured mouse lymphatic endothelial cells. Importantly, treatment of human dermal microvascular endothelial cells with tumor necrosis factor or phorbol 12-myristate 13-acetate resulted in Thy1 upregulation in podoplanin-expressing lymphatic endothelial cells, but not in podoplanin-negative blood vascular endothelial cells. Moreover, adhesion of human polymorphonuclear and mononuclear leukocytes to human lymphatic endothelial cells was Thy1-dependent. Together, these results identify Thy1 as a novel lymphatic vessel expressed gene and suggest its potential role in the cell adhesion processes required for tumor progression and inflammation.