Antibodies to mouse lung capillary endothelium.

Rorvik, Marie C.; Allison, David P.; Hotchkiss, Jon A.; Witschi, Hanspeter; Kennel, Stephen J.

doi:10.1177/36.7.3290332

Cited by 22 publications

(12 citation statements)

References 18 publications

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“…The reasons for this marked difference are not entirely clear. Electron microscopy showed that anti-TM 34 vs anti-TM 201 preferentially binds to endothelial cells in thin vs thick alveolar walls, respectively [20]. In vitro studies showed that anti-TM 201 has higher affinity to TM in endothelial cells, but lesser number of apparent binding sites in endothelial cells vs anti-TM 34 (Fig.2).…”

Section: Discussionmentioning

confidence: 94%

“…Monoclonal antibodies mAb anti-TM34-211 (anti-TM 34 ) and anti-TM201-411 (anti-TM 201 ) are rat antibodies against murine TM, described previously [20][21][22]. A monoclonal antibody raised in rats against human creatine kinase was used as control IgG (ATCC hybridoma, CKMM 14.15, Manassas, VA).…”

Section: Reagentsmentioning

confidence: 99%

“…In this study, we used two different monoclonal antibodies to TM: mAb anti-TM34-211 (anti-TM 34 ) and anti-TM201-411 (anti-TM 201 ), which are directed to distinct TM epitopes and have different affinities for TM [20]. We conjugated GOX to anti-TM mAbs via either a streptavidin cross-linker to produce anti-TM/GOX conjugates (~300 nm diameter), or by coating GOX and anti-TM to the surface of polystyrene beads to produce anti-TM/bead/GOX formulations (~200 nm diameter).…”

Section: Introductionmentioning

confidence: 99%

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Factors modulating the delivery and effect of enzymatic cargo conjugated with antibodies targeted to the pulmonary endothelium

Shuvaev

Christofidou‐Solomidou

Scherpereel

et al. 2007

Journal of Controlled Release

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Vascular drug targeting may improve therapies, yet a thorough understanding of the factors that regulate effects of drugs directed to the endothelium is needed to translate this approach into the clinical domain. To define factors modulating the efficacy and effects of endothelial targeting, we used a model enzyme (glucose oxidase, GOX) coupled with monoclonal antibodies (anti-TM 34 or anti-TM 201 ) to distinct epitopes of thrombomodulin, a surface determinant enriched in the pulmonary endothelium. GOX delivery results in conversion of glucose and oxygen into H 2 O 2 leading to lung damage, a clear physiologic endpoint. Results of in vivo studies in mice showed that the efficiency of cargo delivery and its effect are influenced by a number of factors including: 1) The level of pulmonary uptake of the targeting antibody (anti-TM 201 was more efficient than anti-TM 34 ); 2) The amount of an active drug delivered to the target; 3) The amount of target antigen on the endothelium (animals with suppressed TM levels showed less targeting); and, 4) The substrate availability for the enzyme cargo in the target tissue (hyperoxia augmented GOX-induced injury). Therefore, both activity of the conjugates and biological factors control targeting and effects of enzymatic cargo. Understanding the nature of such "modulating biological factors" will hopefully allow optimization and ultimately applications of drug targeting for "individualized" pharmacotherapy.

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Section: Discussionmentioning

confidence: 94%

Section: Reagentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Factors modulating the delivery and effect of enzymatic cargo conjugated with antibodies targeted to the pulmonary endothelium

Shuvaev

Christofidou‐Solomidou

Scherpereel

et al. 2007

Journal of Controlled Release

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“…MoAbs 273-34A and 411-201B are rat subclass IgG2a, the binding specificities of which have been previously described (Kennel et al 1987, Rorvik et al 1988) Rat MoAb 135-14 (subclass IgGza), used as a negative control, has no known binding specificity.…”

Section: Methodsmentioning

confidence: 99%

Thrombomodulin distribution during murine development

Ford

Wilkinson

Kennel

1993

Roux's Arch Dev Biol

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Thrombomodulin is a transmembrane glycoprotein involved in the regulation of clot formation. Previous work has shown that in the adult mouse, thrombomodulin expression is primarily located on the luminal surface of endothelial cells; whereas during development, thrombomodulin has been localized to the placental parietal endoderm, the neuroepithelium, head mesenchyme, lung bud, and atrium of Day 10.5 post coitum embryos. We examined the expression of thrombomodulin in the adult mouse and throughout murine development from Day 7.5 to Day. 18.5 post coitum. The high expression of thrombomodulin in the lung bud, developing gonads, leptomeninges, and the parietal endoderm in comparison to the expression levels in the adult organs suggest that thrombomodulin may play an important role in development.The submitted manuscript has been authored by a contractor of the U.S. Government under contract No. DE-AC05-840R21400. Accordingly, the U.S. Government retains nonexclusive, royalty-free license to publish or reproduce the published form of this contribution, or allow others to do so, for US Government purposes.

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“…These materials have included methyl cellulose (Fujimoto and Singer, 1988;Tokuyasu, 1980) and Epon 812 (Rorvik et al, 1988). Unfortunately, these agents dry to a thick, uneven coat which obscures much of the ultrastructural detail of the sections.…”

Section: Light Microscopymentioning

confidence: 99%

Lectin and immunolabeling of microvascular endothelia

Milici

Porter

1991

J. Elec. Microsc. Tech.

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A number of recently developed localization techniques are beginning to be applied in the study of endothelial cells and their structural components. In this article we will review a number of these cytochemical approaches as well as their advantages and disadvantages and their applications. The methods will be presented for processing tissues for either L.R. White embedding or semi-thin and thin frozen sections followed by subsequent lectin and immunolabeling for fluorescence and electron microscopic examination. These techniques are easily applied in the localization of perfused exogenous proteins and of endogenous endothelial-associated proteins. The results that can be obtained from such studies are presented and discussed.

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Antibodies to mouse lung capillary endothelium.

Cited by 22 publications

References 18 publications

Factors modulating the delivery and effect of enzymatic cargo conjugated with antibodies targeted to the pulmonary endothelium

Factors modulating the delivery and effect of enzymatic cargo conjugated with antibodies targeted to the pulmonary endothelium

Thrombomodulin distribution during murine development

Lectin and immunolabeling of microvascular endothelia

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