Monoclonal antibodies to angiotensin-converting enzyme: A powerful tool for lung and vessel studies

Danilov, Sergei M.; Sakharov, Ivan Yu.; Martynov, A.; Faerman, Alexander; Muzykantov, Vladimir R.; Klibanov, Alexander L.; Trakht, Ilya

doi:10.1016/0022-2828(89)90853-5

Cited by 11 publications

(4 citation statements)

References 11 publications

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“…The tissue distribution of radiolabeled anti-mouse ACE mAb in mice (Balyasnikova et al, 2006) correlates with ACE expression on the surface of endothelial cells as shown previously for mAbs against rat and human ACE (Danilov et al, 1989). In our studies, 77% percent of intravenously injected ACE mAb was retained in the lung, consistent with the high level of ACE expression in pulmonary microvessel endothelial cells (Danilov et al, 2001; Franke et al, 1997).…”

Section: Discussionsupporting

confidence: 59%

“…Endothelial ACE expression was measured by in vivo radiolabeled mAb binding (Danilov et al 1989, Muzykantov and Danilov, 1995, Balyasnikova et al, 2006) and quantitative immunohistochemistry using a set of mAbs to denatured mouse ACE (Balyasnikova et al, 2005). The approach, based on the lung accumulation of anti-ACE monoclonal antibodies, has been proven to be an early and sensitive method to monitor endothelial dysfunction and lung injury (Danilov et al, 1989, Muzykantov and Danilov 1991, 1995) as shown in various lung injury models (Muzykantov and Danilov, 1995). In the present study, we applied this methodology in combination with classic measures to examine whether the absence of caveolin-1 affects ACE expression in different tissues.…”

Section: Introductionmentioning

confidence: 99%

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Reduced expression of angiotensin I-converting enzyme in Caveolin-1 knockout mouse lungs

Maniatis¹,

Balyasnikova²,

Metzger³

et al. 2010

Microvascular Research

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Reduced lung capillary expression of angiotensin I-converting enzyme (ACE), a key enzyme in cardiovascular pathophysiology, and of caveolin-1, an important regulator of endothelial cell signalling, has been demonstrated in various models of pulmonary arterial hypertension (PAH). We addressed the relationship between PAH and ACE expression in caveolin-1 knockout mice (Cav1 −/− ), which have moderate PAH. Tissue ACE activity was reduced by 50% in lungs from 3-month old Cav1 −/− mice compared to wild type (WT). A similar reduction in lung endothelial ACE expression was observed by measuring the lung uptake of 125 I-labeled monoclonal anti-ACE antibody and by quantitative immunohistochemistry. These alterations in ACE are limited to capillary segments of the pulmonary circulation. Functionally, the increase in pulmonary artery pressure (PAP) in response to ACE conversion of angiotensin I to angiotensin II in isolated, perfused mouse lungs was reduced significantly in Cav1 −/− mice compared to WT. Thus, these complementary approaches demonstrate the dependence of lung microvascular endothelial cell ACE protein expression on caveolin-1 expression and underscore the vital role of caveolin-1-regulated pulmonary vascular homeostasis on endothelial ACE expression and activity. In summary, we have revealed a novel role of caveolin-1 in the regulation of ACE expression in pulmonary capillary endothelial cells. Further understanding of the mechanism by which reduced caveolin-1 expression leads altered pulmonary vascular development, PAH, and reduced ACE expression may have important clinical implications in patients with these severe lung diseases.

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Section: Discussionsupporting

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Reduced expression of angiotensin I-converting enzyme in Caveolin-1 knockout mouse lungs

Maniatis¹,

Balyasnikova²,

Metzger³

et al. 2010

Microvascular Research

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“…One of the mAbs against ACE, obtained in the first series (9B9), recognized not only human ACE, but also rat ACE [32] (and also hamster and cat ACE, although to a much lesser extent [30], which allowed to trace this mAb after intravenous administration. We found (together with Vladimir Muzykantov) that radioactively labeled mAb 9B9 is extremely effective (up to 50% of the administered dose [73] and specificity (30-50 times more than in other organs and blood) accumulate in the lung [74][75][76]. Later we mapped the epitope for mAb 9B9 [42] and also determined the reason for such specific accumulation of mAbs to ACE in the lung.…”

Section: Targeted Drug/gene Delivery Into the Lung Endothelium Using mentioning

confidence: 79%

“…MAb against aminopeptidase P accumulates in the lung with systemic administration even more specifically than mAb against ACE (lung/blood ratio is 124 for mAb 833c [78] versus 23 for mAb 9B9 [73]), so it can be used for gamma-scintigraphy of lung capillaries [78] (along with mAbs against ACE [74,75]. However, the expression of aminopeptidase P in lung capillaries, although very specific, is very low (in comparison with the amount of ACE expressed in human lungsapproximately 20 mg, according to our estimates), which does not allow the use this mAb (833c) for the delivery to the lung therapeutically significant amounts of drugs (proteins, genes, small molecules, particles).…”

Section: Targeted Drug/gene Delivery Into the Lung Endothelium Using mentioning

confidence: 99%

Conformational Fingerprinting Using Monoclonal Antibodies (on the Example of Angiotensin I-Converting Enzyme-ACE)

Danilov

2017

Mol Biol

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⎯During the past 30 years my laboratory has generated 40+ monoclonal antibodies (mAbs) directed to structural and conformational epitopes on human ACE as well as ACE from rats, mice and other species. These mAbs were successfully used for detection and quantification of ACE by ELISA, Western blotting, flow cytometry and immunohistochemistry. In all these applications mainly single mAbs were used. We hypothesized that we can obtain a completely new kind of information about ACE structure and function if we use the whole set of mAbs directed to different epitopes on the ACE molecule. When we finished epitope mapping of all mAbs to ACE (and especially, those recognizing conformational epitopes), we realized that we had obtained a new tool to study ACE. First, we demonstrated that binding of some mAbs is very sensitive to local conformational changes on the ACE surface-due to local denaturation, inactivation, ACE inhibitor or mAbs binding or due to diseases. Second, we were able to detect, localize and characterize several human ACE mutations. And, finally, we established a new concept-conformational fingerprinting of ACE using mAbs that in turn allowed us to obtain evidence for tissue specificity of ACE, which has promising scientific and diagnostic perspectives. The initial goal for the generation of mAbs to ACE 30 years ago was obtaining mAbs to organ-specific endothelial cells, which could be used for organ-specific drug delivery. Our systematic work on characterization of mAbs to numerous epitopes on ACE during these years has lead not only to the generation of the most effective mAbs for specific drug/gene delivery into the lung capillaries, but also to the establishment of the concept of conformational fingerprinting of ACE, which in turn gives a theoretical base for the generation of mAbs, specific for ACE from different organs. We believe that this concept could be applicable for any glycoprotein against which there is a set of mAbs to different epitopes.

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Systemic administration of platelet-activating factor in rat reduces specific pulmonary uptake of circulating monoclonal antibody to angiotensin-converting enzyme

Atochina

Hiemisch

Muzykantov

et al. 1992

Lung

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The biodistribution of radiolabeled mouse monoclonal antibody (MoAb) to angiotensin-converting enzyme (ACE) and control, nonimmune mouse IgG in platelet activating factor (PAF)-treated rats was studied. The blood level of both preparations was slightly decreased (90% of the control) in PAF-treated rats. Specific pulmonary accumulation of anti-ACE MoAb was reduced to 50% of control in contrast to a doubling in nonspecific pulmonary uptake of non-immune IgG. The changes in anti-ACE MoAb biodistribution were lung-specific and were accompanied by decrease in the pulmonary ACE activity (to 60% of control) and increase in serum ACE activity (to 170% of control). Thus anti-ACE MoAb reveals PAF-induced changes in the status of the pulmonary ACE and therefore can be used for the studies of pathology of the pulmonary endothelium.

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Monoclonal antibodies to angiotensin-converting enzyme: A powerful tool for lung and vessel studies

Cited by 11 publications

References 11 publications

Reduced expression of angiotensin I-converting enzyme in Caveolin-1 knockout mouse lungs

Reduced expression of angiotensin I-converting enzyme in Caveolin-1 knockout mouse lungs

Conformational Fingerprinting Using Monoclonal Antibodies (on the Example of Angiotensin I-Converting Enzyme-ACE)

Systemic administration of platelet-activating factor in rat reduces specific pulmonary uptake of circulating monoclonal antibody to angiotensin-converting enzyme

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