Lung uptake of antibodies to endothelial antigens: key determinants of vascular immunotargeting
| Autor: | Katarina Pauls, Timothy McDonald, Folker E. Franke, Sergei M. Danilov, Vitaly D. Gavrilyuk, Vladimir R. Muzykantov, David W. Harshaw, David J. Miletich |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Pulmonary and Respiratory Medicine
Male Pathology medicine.medical_specialty Endothelium Physiology medicine.drug_class medicine.medical_treatment Biology Peptidyl-Dipeptidase A Monoclonal antibody Iodine Radioisotopes Rats Sprague-Dawley Antigen Antibody Specificity Physiology (medical) medicine Animals Tissue Distribution Lung Antibodies Monoclonal Cell Biology Immunotherapy Intercellular Adhesion Molecule-1 Antigens Differentiation Immunohistochemistry Capillaries Rats Endothelial stem cell Platelet Endothelial Cell Adhesion Molecule-1 medicine.anatomical_structure Circulatory system Immunology Injections Intravenous Thy-1 Antigens Endothelium Vascular Blood vessel |
| Zdroj: | American journal of physiology. Lung cellular and molecular physiology. 280(6) |
| ISSN: | 1040-0605 |
| Popis: | Vascular immunotargeting is a mean for a site-selective delivery of drugs and genes to endothelium. In this study, we compared recognition of pulmonary and systemic vessels in rats by candidate carrier monoclonal antibodies (MAbs) to endothelial antigens platelet endothelial cell adhesion molecule (PECAM)-1 (CD31), intercellular adhesion molecule (ICAM)-1 (CD54), Thy-1.1 (CD90.1), angiotensin-converting enzyme (ACE; CD143), and OX-43. Tissue immunostaining showed that endothelial cells were Thy-1.1 positive in capillaries but negative in large vessels. In the lung, anti-ACE MAb provided a positive staining in 100% capillaries vs. 5–20% capillaries in other organs. Other MAbs did not discriminate between pulmonary and systemic vessels. We determined tissue uptake after infusion of 1 μg of125I-labeled MAbs in isolated perfused lungs (IPL) or intravenously in intact rats. Uptake in IPL attained 46% of the injected dose (ID) of anti-Thy-1.1 and 20–25% ID of anti-ACE, anti-ICAM-1, and anti-OX-43 (vs. 0.5% ID of control IgG). However, after systemic injection at this dose, only anti-ACE MAb 9B9 displayed selective pulmonary uptake (16 vs. 1% ID/g in other organs). Anti-OX-43 displayed low pulmonary (0.5% ID/g) but significant splenic and cardiac uptake (7 and 2% ID/g). Anti-Thy-1.1 and anti-ICAM-1 displayed moderate pulmonary (4 and 6% ID/g, respectively) and high splenic and hepatic uptake (e.g., 18% ID/g of anti-Thy-1.1 in spleen). The lung-to-blood ratio was 5, 10, and 15 for anti-Thy-1.1, anti-ACE, and anti-ICAM-1, respectively. PECAM antibodies displayed low pulmonary uptake in perfusion (2% ID) and in vivo (3–4% ID/g). However, conjugation with streptavidin (SA) markedly augmented pulmonary uptake of anti-PECAM in perfusion (10–54% ID, depending on an antibody clone) and in vivo (up to 15% ID/g). Therefore, ACE-, Thy-1.1-, ICAM-1-, and SA-conjugated PECAM MAbs are candidate carriers for pulmonary targeting. ACE MAb offers a high selectivity of pulmonary targeting in vivo, likely because of a high content of ACE-positive capillaries in the lungs. |
| Databáze: | OpenAIRE |
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