Aminopeptidase P – a Cell-Surface Antigen of Endothelial and Lymphoid Cells: Catalytic and Immuno-Histotopical Evidences

Lasch, Jürgen; Moschner, Sylke; Sann, H.; Zellmer, Sebastian; Koelsch, R

doi:10.1515/bchm.1998.379.6.705

Cited by 22 publications

(11 citation statements)

References 8 publications

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“…For the specific detection of blood endothelial cells, we used here a monoclonal antibody, designated JG12, and we provide evidence that the corresponding antigen is the enzyme aminopeptidase P, a bradykinin-degrading membrane peptidase (18) that was previously associated with endothelial cells in lung, kidney, brain, and intestine by others (19). Aminopeptidase P is a glycosyl-phosphatidylinositol (GPI) membrane-linked aminoacylproline aminopeptidase specific for N-terminal Xaaproline bonds and can inactivate bradykinin by cleaving the Arg 1 -Pro 2 bond (18).…”

Section: Discussionmentioning

confidence: 99%

Lymphatic Microvessels in the Rat Remnant Kidney Model of Renal Fibrosis

Matsui

Nagy-Bojarsky

Laakkonen

et al. 2003

Journal of the American Society of Nephrology

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Abstract. Rat remnant kidney is an established model of renal tubulointerstitial fibrosis and progression to end-stage renal failure. The morphologic lesions comprise nephron loss and regeneratory tubular hypertrophy, interstitial infiltration, predominately by macrophages, and progressive fibrosis. A critical role in this complex pathology was assigned to tubulointerstitial blood microvessels that regulate the supply of oxygen and nutrients of tubuli. Whereas some investigations reported a rarefaction of the vascular network in association with the degenerative cortical changes, others observed an increase in vascularization. Here these discrepant findings are addressed by reinvestigation of the vascularization of rat remnant kidneys by the use of two novel endothelial lineage specific, discriminatory markers, i.e., the membrane mucoprotein podoplanin with specificity for lymphatic endothelia, and the glycosylphosphatidylinositol (GPI)-anchored membrane enzyme aminopeptidase P that is recognized by a monoclonal antibody designated JG12 and that is specifically expressed by endothelial cells of blood vessels only. The results obtained confirm a regional rarefaction of aminopeptidase P-positive blood microvessels; they also establish major changes in the renal lymphatic vasculature. Massive proliferation of lymphatic vessels was observed in fibrotic tubulointerstitial regions, whereas in kidneys of sham-operated rats, only a few lymphatic vessels were found adjoined with arteries. The lymphatic vessels frequently contained mononuclear cells that were also encountered in the interstitial spaces and expressed relative large amounts of vascular endothelial growth factor-C mRNA by in situ hybridization. Collectively, these results indicate that a large proportion of the microvessels encountered in the cortex of remnant kidneys are of lymphatic origin and cannot be discriminated by common endothelial markers, such as CD34, that are expressed by both lymphatic and blood endothelia cells. As lymphatic endothelial cells secrete chemokines that attract dendritic cells, it is possible that the increase in lymphatic vascularization could enhance the immunologic surveillance of remnant kidneys.

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Section: Discussionmentioning

confidence: 99%

Lymphatic Microvessels in the Rat Remnant Kidney Model of Renal Fibrosis

Matsui

Nagy-Bojarsky

Laakkonen

et al. 2003

Journal of the American Society of Nephrology

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“…APaseP is a GPI-linked membrane protein expressed on the surface of vascular endothelial cells in various tissues, on lymphoid cells, and on the brush-border membrane in the intestine and in kidney tubules (20). Potential physiological substrates for APaseP include interleukins and bradykinin (30).…”

Section: Discussionmentioning

confidence: 99%

“…Anti-APaseP antibody was a gift of J. Lasch, University of Halle, Germany (20). ICR CD-1 mice were purchased from Harlan Sprague-Dawley.…”

Section: Methodsmentioning

confidence: 99%

Molecular specialization of breast vasculature: A breast-homing phage-displayed peptide binds to aminopeptidase P in breast vasculature

Essler

Ruoslahti

2002

Proc. Natl. Acad. Sci. U.S.A.

175

103

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In vivo phage display identifies peptides that selectively home to the vasculature of individual organs, tissues, and tumors. Here we report the identification of a cyclic nonapeptide, CPGPE-GAGC, which homes to normal breast tissue with a 100-fold selectivity over nontargeted phage. The homing of the phage is inhibited by its cognate synthetic peptide. Phage localization in tissue sections showed that the breast-homing phage binds to the blood vessels in the breast, but not in other tissues. The phage also bound to the vasculature of hyperplastic and malignant lesions in transgenic breast cancer mice. Expression cloning with a phage-displayed cDNA library yielded a phage that specifically bound to the breast-homing peptide. The cDNA insert was homologous to a fragment of aminopeptidase P. The homing peptide bound aminopeptidase P from malignant breast tissue in affinity chromatography. Antibodies against aminopeptidase P inhibited the in vitro binding of the phage-displayed cDNA to the peptide and the in vivo homing of phage carrying the peptide. These results indicate that aminopeptidase P is the receptor for the breast-homing peptide. This peptide may be useful in designing drugs for the prevention and treatment of breast cancer.endothelial cells ͉ vascular targeting ͉ breast cancer T he vascular beds of individual tissues differ in structure and metabolic function, and in expression of organ-specific adhesion molecules (1). Such specialization is particularly striking in lymphoid tissues where the high endothelia are composed of cells that express unique adhesion molecules for lymphocyte homing (2). Furthermore, metastasis into preferred organs by certain tumors may depend on interactions between tumor cells and organ-specific molecules in the vasculature of the target organ (3).Our laboratory has shown that peptide libraries displayed on phage can be screened in vivo for phage that home to a specific target, and we and others have shown that peptides capable of homing to the vasculature of various individual tissues can be isolated in this manner (4 -6). In vivo selections have also successfully identified peptides that home to tumor vasculature and the vasculature of other pathological lesions (7,8). Some of the tumor-homing peptides recognize known markers of sprouting endothelial cells and angiogenic tumor vasculature, such as the ␣ v ␤ 3 , ␣ v ␤ 5 , and ␣ 5 ␤ 1 integrins (7, 9), matrix metalloproteases (10 -12), and NG2 proteoglycan (13,14). A group of tumor-homing peptides containing the sequence motif NGR were used to identify aminopeptidase N as a new marker of angiogenic vasculature (15). Only one homing peptide receptor in the vasculature of normal tissues has been identified so far; membrane dipeptidase is selectively expressed in lung vasculature and serves as a receptor for a set of lung-homing peptides (16).Homing peptides show promise in the delivery of drugs and other therapies into designated target sites. Thus, peptides identified by phage display have been used to target doxorubicin, proap...

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“…Thus, the amount of detergents to be employed may be reduced, aggregation and precipitation of hydrophobic proteins minimized, and low-abundant proteins enriched. Yet, irrespective of these advantages, merely soluble but no membrane proteins have been resolved by FF-IEF up to now [13][14][15][16][17].…”

Section: The Fractionation Of Hydrophobic Proteins Is Still An Intrigmentioning

confidence: 99%

“…An entirely new impetus was given to FF-IEF in the last years by the introduction of Prolytes  , novel detergents, reducing and denaturing agents as well as of refined implements like the OCTOPUS instrument (Dr. Weber GmbH, Ismaning, Germany) and its successor, the Pro Team FFE  (TECAN, Männedorf, Switzerland). This is documented by the numerous reports on the successful separation of soluble proteins [13][14][15][16][17], which consequently raises the question whether integral membrane proteins can be also fractionated by FF-IEF without precipitation and other shortcomings known from gel-based IEF.…”

Section: Introductionmentioning

confidence: 99%

Efficient separation and analysis of peroxisomal membrane proteins using free‐flow isoelectric focusing

Weber¹,

Islinger²,

Weber³

et al. 2004

Electrophoresis

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We have elaborated a protocol for the fractionation of both hydrophilic and hydrophobic proteins using as a model the matrix and membrane compartments of highly purified rat liver peroxisomes because of their distinct proteomes and characteristic composition with a high quota of basic proteins. To keep highly hydrophobic proteins in solution, an urea/thiourea/detergent mixture, as used in traditional gel-based isoelectric focusing (IEF), was added to the electrophoresis buffer. Electrophoresis was conducted in the ProTeam free-flow electrophoresis (FFE) apparatus of TECAN separating proteins into 96 fractions on a pH 3-12 gradient. Consecutive sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis demonstrated that both matrix and the integral membrane proteins of peroxisomes could be successfully fractionated and then identified by mass spectrometry. This is documented by the detection of PMP22, which is the most hydrophobic and basic protein of the peroxisomal membrane with a pI > 10. The identification of 96 prominent spots corresponding to polypeptides with different physical and chemical properties, e.g., the most abundant integral membrane polypeptides of peroxisomes and specific ones of the mitochondrial and microsomal membrane, reflects the fractionation potential of free-flow (FF)-IEF, accentuating its value in proteomic research as an alternative perhaps superior to gel-based IEF.

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Aminopeptidase P – a Cell-Surface Antigen of Endothelial and Lymphoid Cells: Catalytic and Immuno-Histotopical Evidences

Cited by 22 publications

References 8 publications

Lymphatic Microvessels in the Rat Remnant Kidney Model of Renal Fibrosis

Lymphatic Microvessels in the Rat Remnant Kidney Model of Renal Fibrosis

Molecular specialization of breast vasculature: A breast-homing phage-displayed peptide binds to aminopeptidase P in breast vasculature

Efficient separation and analysis of peroxisomal membrane proteins using free‐flow isoelectric focusing

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