Heparin Interaction with the Primed Polymorphonuclear Leukocyte CD11b Induces Apoptosis and Prevents Cell Activation
Heparin is known to have anti-inflammatory effects, yet the mechanisms are not completely understood. In this study, we tested the hypothesis that heparin has a direct effect on activated polymorphonuclear leukocytes (PMNLs), changing their activation state, and can explain its anti-inflammatory eff...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2015/751014 |
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| _version_ | 1832551255389503488 |
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| author | Meital Cohen-Mazor Rafi Mazor Batya Kristal Erik B. Kistler Inbal Ziv Judith Chezar Shifra Sela |
| author_facet | Meital Cohen-Mazor Rafi Mazor Batya Kristal Erik B. Kistler Inbal Ziv Judith Chezar Shifra Sela |
| author_sort | Meital Cohen-Mazor |
| collection | DOAJ |
| description | Heparin is known to have anti-inflammatory effects, yet the mechanisms are not completely understood. In this study, we tested the hypothesis that heparin has a direct effect on activated polymorphonuclear leukocytes (PMNLs), changing their activation state, and can explain its anti-inflammatory effect. To test our hypothesis, we designed both in vitro and ex vivo studies to elucidate the mechanism by which heparin modulates PMNL functions and therefore the inflammatory response. We specifically tested the hypothesis that priming of PMNLs renders them more susceptible to heparin. Amplified levels of CD11b and increased rate of superoxide release manifested PMNL priming. Increase in cell priming resulted in a dose-dependent increase in heparin binding to PMNLs followed by augmented apoptosis. Blocking antibodies to CD11b inhibited heparin binding and abolished the apoptotic response. Moreover, heparin caused a significant dose-dependent decrease in the rate of superoxide release from PMNLs, which was blunted by blocking antibodies to CD11b. Altogether, this study shows that the interaction of heparin with the PMNL CD11b results in cell apoptosis and explains heparin’s anti-inflammatory effects. |
| format | Article |
| id | doaj-art-66425e3c839d4f2fb2fffc83f74e253f |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-66425e3c839d4f2fb2fffc83f74e253f2025-02-03T06:01:54ZengWileyJournal of Immunology Research2314-88612314-71562015-01-01201510.1155/2015/751014751014Heparin Interaction with the Primed Polymorphonuclear Leukocyte CD11b Induces Apoptosis and Prevents Cell ActivationMeital Cohen-Mazor0Rafi Mazor1Batya Kristal2Erik B. Kistler3Inbal Ziv4Judith Chezar5Shifra Sela6Eliachar Research Laboratory, Western Galilee Hospital, 22100 Nahariya, IsraelEliachar Research Laboratory, Western Galilee Hospital, 22100 Nahariya, IsraelTechnion Faculty of Medicine, 3525433 Haifa, IsraelDepartment of Anesthesiology & Critical Care, VA San Diego Healthcare System, San Diego, CA 92161, USAEliachar Research Laboratory, Western Galilee Hospital, 22100 Nahariya, IsraelHematology Laboratory, Western Galilee Hospital, 22100 Nahariya, IsraelEliachar Research Laboratory, Western Galilee Hospital, 22100 Nahariya, IsraelHeparin is known to have anti-inflammatory effects, yet the mechanisms are not completely understood. In this study, we tested the hypothesis that heparin has a direct effect on activated polymorphonuclear leukocytes (PMNLs), changing their activation state, and can explain its anti-inflammatory effect. To test our hypothesis, we designed both in vitro and ex vivo studies to elucidate the mechanism by which heparin modulates PMNL functions and therefore the inflammatory response. We specifically tested the hypothesis that priming of PMNLs renders them more susceptible to heparin. Amplified levels of CD11b and increased rate of superoxide release manifested PMNL priming. Increase in cell priming resulted in a dose-dependent increase in heparin binding to PMNLs followed by augmented apoptosis. Blocking antibodies to CD11b inhibited heparin binding and abolished the apoptotic response. Moreover, heparin caused a significant dose-dependent decrease in the rate of superoxide release from PMNLs, which was blunted by blocking antibodies to CD11b. Altogether, this study shows that the interaction of heparin with the PMNL CD11b results in cell apoptosis and explains heparin’s anti-inflammatory effects.http://dx.doi.org/10.1155/2015/751014 |
| spellingShingle | Meital Cohen-Mazor Rafi Mazor Batya Kristal Erik B. Kistler Inbal Ziv Judith Chezar Shifra Sela Heparin Interaction with the Primed Polymorphonuclear Leukocyte CD11b Induces Apoptosis and Prevents Cell Activation Journal of Immunology Research |
| title | Heparin Interaction with the Primed Polymorphonuclear Leukocyte CD11b Induces Apoptosis and Prevents Cell Activation |
| title_full | Heparin Interaction with the Primed Polymorphonuclear Leukocyte CD11b Induces Apoptosis and Prevents Cell Activation |
| title_fullStr | Heparin Interaction with the Primed Polymorphonuclear Leukocyte CD11b Induces Apoptosis and Prevents Cell Activation |
| title_full_unstemmed | Heparin Interaction with the Primed Polymorphonuclear Leukocyte CD11b Induces Apoptosis and Prevents Cell Activation |
| title_short | Heparin Interaction with the Primed Polymorphonuclear Leukocyte CD11b Induces Apoptosis and Prevents Cell Activation |
| title_sort | heparin interaction with the primed polymorphonuclear leukocyte cd11b induces apoptosis and prevents cell activation |
| url | http://dx.doi.org/10.1155/2015/751014 |
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