| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Bledzka, Kamila M. Ballantyne, Christie M. Soloviev, Dmitry A. Hazen, Stanley L. Szpak, Dorota Pluskota, Elzbieta Plow, Edward F. |
| Description |
Author Affiliation: Soloviev DA ( Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Learner Research Institute, Cleveland Clinic, Cleveland, OH 44195); Hazen SL ( Department of Molecular and Cellular Medicine, Cleveland Clinic, Cleveland, OH 44195); Szpak D ( Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Learner Research Institute, Cleveland Clinic, Cleveland, OH 44195); Bledzka KM ( Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Learner Research Institute, Cleveland Clinic, Cleveland, OH 44195); Ballantyne CM ( Baylor College of Medicine and Methodist DeBakey Heart and Vascular Center, Houston, TX 77030.); Plow EF ( Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Learner Research Institute, Cleveland Clinic, Cleveland, OH 44195); Pluskota E ( Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Learner Research Institute, Cleveland Clinic, Cleveland, OH 44195) |
| Abstract |
Polymorphonuclear neutrophils (PMNs) and macrophages are crucial contributors to neovascularization, serving as a source of chemokines, growth factors, and proteases. (M)ß(2)(CD11b/CD18) and (L)ß(2)(CD11a/CD18) are expressed prominently and have been implicated in various responses of these cell types. Thus, we investigated the role of these ß2 integrins in angiogenesis. Angiogenesis was analyzed in wild-type (WT), (M)-knockout ( (M)(-/-)), and (L)-deficient ( (L)(-/-)) mice using B16F10 melanoma, RM1 prostate cancer, and Matrigel implants. In all models, vascular area was decreased by 50-70% in (M)(-/-) mice, resulting in stunted tumor growth as compared with WT mice. In contrast, (L) deficiency did not impair angiogenesis and tumor growth. The neovessels in (M)(-/-) mice were leaky and immature because they lacked smooth muscle cell and pericytes. Defective angiogenesis in the (M)(-/-) mice was associated with attenuated PMN and macrophage recruitment into tumors. In contrast to WT or the (L)(-/-) leukocytes, the (M)(-/-) myeloid cells showed impaired plasmin (Plm)-dependent extracellular matrix invasion, resulting from 50-75% decrease in plasminogen (Plg) binding and pericellular Plm activity. Surface plasmon resonance verified direct interaction of the (M)I-domain, the major ligand binding site in the ß(2) integrins, with Plg. However, the (L)I-domain failed to bind Plg. In addition, endothelial cells failed to form tubes in the presence of conditioned medium collected from TNF- -stimulated PMNs derived from the (M)(-/-) mice because of severely impaired degranulation and secretion of VEGF. Thus, (M)ß(2) plays a dual role in angiogenesis, supporting not only Plm-dependent recruitment of myeloid cells to angiogenic niches, but also secretion of VEGF by these cells. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| DOI |
10.4049/jimmunol.1400202 |
| Journal |
The Journal of Immunology |
| Issue Number |
9 |
| Volume Number |
193 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2014-11-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Leukocytes Immunology Metabolism Macrophage-1 Antigen Genetics Neovascularization, Pathologic Animals Bone Marrow Transplantation Chemotaxis Disease Models, Animal Macrophages Melanoma, Experimental Pathology Mice Mice, Knockout Neutrophils Plasminogen Prostatic Neoplasms Protein Binding Tumor Burden Vascular Endothelial Growth Factor A Biosynthesis Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
