A novel system for investigating the ability of smooth muscle cells and fibroblasts to regulate adhesion of flowing leukocytes to endothelial cells

Rainger, G. Ed; Stone, P.C.W.; Morland, Clare M.; Nash, Gerard B.

doi:10.1016/s0022-1759(01)00427-6

Cited by 59 publications

(67 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In association with our current findings, this suggests that such microenvironmental signals are important in many contexts. 11,12 Modulation of endothelium by coculture with hepatocytes was demonstrated previously in an animal model in which rat liver implanted onto the chorioallantoic membrane of quail embryos converted the quail microvessels to a sinusoidal phenotype. 31 Our experiments now show that hepatocytes also can affect the ability of liver endothelium to recruit lymphocytes directly by modulating adhesive interactions.…”

Section: Discussionmentioning

confidence: 91%

“…To simulate liver architecture accurately and to determine the role of paracrine interactions in lymphocyte adhesion, we adapted our previously described flow-based coculture model to study lymphocyte adhesion to sinusoidal endothelium in the presence of hepatocytes. [11][12][13] This novel multicellular in vitro model allowed us to demonstrate that hepatocytes can modulate the recruitment of lymphocytes directly via overlying sinusoidal endothelium. These observations have major implications for the microenvironmental regulation of constitutive lymphocyte trafficking and inflammatory liver disease.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Lymphocyte traffic through sinusoidal endothelial cells is regulated by hepatocytes

et al. 2005

Self Cite

View full text Add to dashboard Cite

Crosstalk between hepatic sinusoidal ECs and closely juxtaposed hepatocytes via vascular endothelial growth factor is essential for the maintenance of sinusoidal endothelial growth and differentiation. We propose that paracrine interactions between endothelial cells and hepatocytes also may be responsible for the unique complement of adhesion receptors expressed on sinusoidal endothelium that regulate the recruitment of lymphocytes into the liver. To address this hypothesis, we developed an in vitro model of the hepatic sinusoid in which flowing lymphocytes could interact with hepatic endothelium conditioned by the presence of hepatocytes. Human hepatic sinusoidal endothelial cells cocultured with hepatocytes were activated so that they supported the adhesion of lymphocytes at levels equivalent to those seen on endothelium stimulated with the inflammatory cytokine tumour necrosis factor-␤.

show abstract

Section: Discussionmentioning

confidence: 91%

mentioning

confidence: 99%

Lymphocyte traffic through sinusoidal endothelial cells is regulated by hepatocytes

et al. 2005

Self Cite

View full text Add to dashboard Cite

show abstract

“…PBMC were isolated by centrifugation of blood on Histopaque 1077 (Sigma-Aldrich, Poole, U.K.), and PBL were prepared by panning of PBMC on culture plastic to remove monocytes (15). In some experiments, CD4 + memory (CD45RA 2 ) T cells were purified from PBMC using a positive selection immunobead kit (Miltenyi Biotec, Surrey, U.K.).…”

Section: Methodsmentioning

confidence: 99%

Prostaglandin D2 Regulates CD4+ Memory T Cell Trafficking across Blood Vascular Endothelium and Primes These Cells for Clearance across Lymphatic Endothelium

Ahmed

McGettrick

Yates

et al. 2011

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Memory lymphocytes support inflammatory and immune responses. To do this, they enter tissue via blood vascular endothelial cells (BVEC) and leave tissue via lymphatic vascular endothelial cells (LVEC). In this study, we describe a hierarchy of signals, including novel regulatory steps, which direct the sequential migration of human T cells across the blood and the lymphatic EC. Cytokine-stimulated (TNF and IFN) human BVEC preferentially recruited memory T cells from purified PBL. Lymphocyte recruitment from flow could be blocked using a function-neutralizing Ab against CXCR3. However, a receptor antagonist directed against the PGD2 receptor DP2 (formerly chemoattractant receptor-homologous molecule expressed on Th2 cells) inhibited transendothelial migration, demonstrating that the sequential delivery of the chemokine and prostanoid signals was required for efficient lymphocyte recruitment. CD4+ T cells recruited by BVEC migrated with significantly greater efficiency across a second barrier of human LVEC, an effect reproduced by the addition of exogenous PGD2 to nonmigrated cells. Migration across BVEC or exogenous PGD2 modified the function, but not the expression, of CCR7, so that chemotaxis toward CCL21 was significantly enhanced. Thus, chemokines may not regulate all stages of lymphocyte migration during inflammation, and paradigms describing their trafficking may need to account for the role of PGD2.

show abstract

“…To evaluate the hypothesis that adhesion is associated with stimulation of PLD activity, the level of adhesion of primary human PMN to fibronectin-coated tissue culture wells was first determined using the fluorescent cellular label, calcein (60,66). FN is a 440,000-kDa protein present in the extracellular matrix (ECM) and plasma which promotes the adhesion of multiple cell types, including PMN, under both physiologic and pathologic conditions (6,7,67,68).…”

Section: Pld Activity Is Increased During Adhesion Of Primary Human Nmentioning

confidence: 99%

Phospholipase D1 Regulates Phagocyte Adhesion

Iyer¹,

Agrawal²,

Thompson³

et al. 2006

The Journal of Immunology

View full text Add to dashboard Cite

Adhesion is a fundamental cellular response that is essential to the physiologic processes of development, differentiation, proliferation, and motility, as well as to the pathology of inflammation,transformation, and metastasis. Adhesion of phagocytic leukocytes is a critical modulator of antimicrobial and cytotoxic functions, including the respiratory burst, secretion, and apoptosis. Since phospholipase D (PLD) is linked to several signaling pathways implicated in these processes, we tested the hypothesis that PLD regulates phagocyte adhesion. Using the fluorescent cellular label, calcein, we found that adhesion of primary human neutrophils and monocyte‐derived macrophages to fibronectin was accompanied by marked stimulation of PLD activity. Similarly, adhesion of both human (PLB, THP‐1) and murine (RAW) myeloid‐macrophage cell lines to fibronectin, fibrinogen, collagen or plastic resulted in significant activation of PLD. Stimulation of PLD activity was rapid and persisted for at least 90 min. Confocal microscopy demonstrated that PLD1 colocalized with actin filaments in adherent phagocytes, in proximity to the focal adhesion proteins, paxillin and talin. Reductions in PLD activity by chemical inhibitors or specific siRNA‐induced knockdown of PLD1 resulted in significant inhibition of phagocyte adhesion. This was accompanied by decreased polymerization of actin at the adhesion interface and reductions in total cellular F‐actin, quantitated using TRITC‐ phalloidin. These data support the hypothesis that PLD1 regulates the initial stages of phagocyte adhesion via promotion of actin polymerization and suggest that stimulation of PLD activity may promote adhesion‐dependent effector responses. Studies supported by NIH GM62302 and AI0559126, and VA Merit Review grants to DJK.

show abstract

A novel system for investigating the ability of smooth muscle cells and fibroblasts to regulate adhesion of flowing leukocytes to endothelial cells

Cited by 59 publications

References 20 publications

Lymphocyte traffic through sinusoidal endothelial cells is regulated by hepatocytes

Lymphocyte traffic through sinusoidal endothelial cells is regulated by hepatocytes

Prostaglandin D2 Regulates CD4+ Memory T Cell Trafficking across Blood Vascular Endothelium and Primes These Cells for Clearance across Lymphatic Endothelium

Phospholipase D1 Regulates Phagocyte Adhesion

Contact Info

Product

Resources

About