Microvascular endothelial cell heterogeneity: Interactions with leukocytes and tumor cells

Belloni, Paula; Tressler, Robert

doi:10.1007/bf00052608

Cited by 93 publications

(42 citation statements)

References 223 publications

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“…There are other reports on tissue-selective molecular differences in endothelia (27). Possibly related to our findings on specific phage homing to the lung, dipeptidyl peptidase has been found to be expressed selectively in the lung endothelium and to serve as the receptor for a lung-metastasizing tumor cell line (28).…”

Section: Discussionsupporting

confidence: 85%

Molecular heterogeneity of the vascular endothelium revealed by in vivo phage display.

Rajotte¹,

Arap²,

Hagedorn³

et al. 1998

J. Clin. Invest.

427

287

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Vascular beds are known to differ in structure and metabolic function, but less is known about their molecular diversity. We have studied organ-specific molecular differences of the endothelium in various tissues by using in vivo screening of peptide libraries expressed on the surface of a bacteriophage. We report here that targeting of a large number of tissues with this method yielded, in each case, phage that homed selectively to the targeted organ. Different peptide motifs were recovered from each of these tissues. The enrichment in homing to the target organs relative to an unselected phage was 3-35-fold. Peptide sequences that conferred selective phage homing to the vasculature of lung, skin, and pancreas were characterized in detail. Immunohistochemistry showed that the phage localized in the blood vessels of their target organ. When tested, the phage homing was blocked in the presence of the cognate peptide. By targeting several tissues and by showing that specific homing could be achieved in each case, we provide evidence that organ-and tissue-specific molecular heterogeneity of the vasculature is a general, perhaps even universal, phenomenon. Our results also show that these molecular differences can serve as molecular addresses. ( J. Clin. Invest.

show abstract

Section: Discussionsupporting

confidence: 85%

Molecular heterogeneity of the vascular endothelium revealed by in vivo phage display.

Rajotte¹,

Arap²,

Hagedorn³

et al. 1998

J. Clin. Invest.

427

287

View full text Add to dashboard Cite

show abstract

“…Endothelial cells are known to be phenotypically heterogeneous in a manner that varies not only with vessel size (31,32) but also within microvascular populations (33)(34)(35)(36)(37). Our results support this: RMEC constitutively express HLA-DR in vivo, whereas endothelial cells from larger vessels do not; lower levels of CD31 on cultured RMEC distinguish them from HUVEC and cultured human lung microvascular endothelial cells; vWF expression is variable within a population of RMEC that otherwise have a uniform phenotype.…”

Section: Discussionsupporting

confidence: 73%

Normal Human Kidney HLA-DR–Expressing Renal Microvascular Endothelial Cells

Muczynski¹,

Ekle²,

Coder³

et al. 2003

Journal of the American Society of Nephrology

144

107

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Abstract. Human, but not murine, renal peritubular and glomerular capillaries constitutively express class II major histocompatibility (MHC) proteins at high levels in normal human kidney. Expression of class II proteins on renal microvascular endothelial cells (RMEC) makes it available to circulating lymphocytes and imparts a surveillance capacity to RMEC for controlling inflammatory responses. In this report, the coexpression of HLA-DR and the endothelial marker CD31 are used to identify RMEC as a distinct population of cells within a standard renal biopsy using flow cytometry. A three-laser, multicolor flow cytometry analysis using Alexa dyes, developed for characterizing the expression of cell surface antigens, identifies RMEC as a population separate from HLA-DRexpressing leukocytes. HLA-DR RMEC co-express HLA-DP and HLA-DQ. RMEC also express the T cell costimulatory factor CD58 but not CD80, CD86, or CD40. On the basis of high HLA-DR expression, RMEC are isolated for culture using fluorescence-activated cell sorting and magnetic beads. Cultured RMEC require normal basal physiologic concentrations of gamma interferon (␥IFN) to maintain HLA protein expression. This expression is regulated by CIITA, the MHC class II-specific transcription factor. Four tissue-specific promoters have been described for CIITA. In freshly isolated RMEC, RT-PCR and hybridization using specific oligonucleotide probes to CIITA promoter sequences identify only the statinsensitive ␥IFN-induced promoter IV of CIITA. Therefore, the constitutive expression of HLA-DR on RMEC in normal human kidney is located in a position for immune surveillance, depends on basal physiologic concentrations of ␥IFN, and may be amenable to regulation with statins.MHC proteins are of two classes distinguished on the basis of structure and function. Class I molecules, composed of a polymorphic subunit complexed with ␤-2-microglobulin, are found on all nucleated cells and present antigenic peptides to CD8ϩ T lymphocytes; class II molecules, composed of polymorphic ␣ and ␤ chains, are constitutively expressed on a limited number of cell types (dendritic cells, macrophages, B lymphocytes) and present antigenic peptides to CD4 ϩ T lymphocytes. We recently described an unusual expression of MHC class II proteins in normal human kidneys that is not found in murine kidneys (1). The human MHC class II protein HLA-DR is abundantly expressed on peritubular and glomerular capillary endothelial cells but not on endothelial cells of larger blood vessels of normal kidney. Antibodies to HLA-DR and CD31, a protein highly expressed on endothelial cells, co-localize on peritubular and glomerular cells within sections of kidney tissue, indicating capillary endothelial cell location of HLA-DR. HLA-DR has also been identified on rare scattered circulating leukocytes found within the kidney, but over 98% of the DR identified by immunofluorescence microscopy in kidney cortex is located on capillary endothelial cells (1). We refer to these cells co-expressing HLA-DR and CD31 as rena...

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“…Their initial arrest and attachment to vascular endothelium precedes their extravasation from the blood stream and is a crucial step in the metastatic cascade (1,2). Tumor cell extravasation is equivalent, in many respects, to the entry of normal circulating cells into inflammatory tissue (3,4). As documented by intravital microscopy, during inflammation, leukocytes begin to interact with the endothelium by first rolling along the vascular wall, then adhering to endothelial cells (EC)' (5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Rolling and adhesion of human tumor cells on vascular endothelium under physiological flow conditions.

Giavazzi¹,

Foppolo²,

Dossi³

et al. 1993

J. Clin. Invest.

205

157

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Microvascular endothelial cell heterogeneity: Interactions with leukocytes and tumor cells

Cited by 93 publications

References 223 publications

Molecular heterogeneity of the vascular endothelium revealed by in vivo phage display.

Molecular heterogeneity of the vascular endothelium revealed by in vivo phage display.

Normal Human Kidney HLA-DR–Expressing Renal Microvascular Endothelial Cells

Rolling and adhesion of human tumor cells on vascular endothelium under physiological flow conditions.

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