Maximal PDGF-induced lung fibroblast chemotaxis requires PDGF receptor-alpha
| Autor: | James C. Bonner, Alvaro Osornio-Vargas, P. M. Lindroos, P. G. Coin, N. A. Hernandez-Rodriguez, A. Badgett |
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| Rok vydání: | 1996 |
| Předmět: |
Male
Pulmonary and Respiratory Medicine medicine.medical_specialty Platelet-derived growth factor Physiology medicine.medical_treatment Becaplermin Binding Competitive Rats Sprague-Dawley chemistry.chemical_compound Physiology (medical) Internal medicine medicine Animals Receptors Platelet-Derived Growth Factor Fibroblast Receptor Lung Platelet-Derived Growth Factor Binding Sites biology Fibroblast chemotaxis Chemotaxis Growth factor Neomycin Proto-Oncogene Proteins c-sis Cell Biology Fibroblasts Rats Cell biology Endocrinology medicine.anatomical_structure chemistry Mitogen-activated protein kinase biology.protein Platelet-derived growth factor receptor Interleukin-1 |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 271:L93-L99 |
| ISSN: | 1522-1504 1040-0605 |
| DOI: | 10.1152/ajplung.1996.271.1.l93 |
| Popis: | Alteration of the platelet-derived growth factor (PDGF) receptor system could be important in enhancing the mitogenic and chemotactic potential of lung fibroblasts during pulmonary fibrogenesis. We previously reported that interleukin-1 beta (IL-1 beta) upregulates the PDGF receptor-alpha (PDGFR-alpha) gene, and in this study we sought to establish the importance of the PDGFR-alpha relative to the PDGFR-beta in mediating a chemotactic response to PDGF-AA, -AB, and -BB. Pretreatment of fibroblasts for 24 h with IL-1 beta increased chemotaxis to all three PDGF isoforms. IL-1 beta pretreatment markedly increased the maximal number of 125I-labeled PDGF-AA binding sites but did not change the number of 125I-PDGF-AB or PDGF-BB sites. However, IL-1 beta increased 125I-PDGFR-AB affinity twofold. Neomycin (5 mM) was used as a PDGFR-alpha antagonist and completely blocked 125I-PDGF-AA binding and PDGF-AA-induced chemotaxis. The binding affinity of 125I-PDGF-AB and 125I-PDGF-BB was increased two-to threefold by neomycin, and chemotaxis to PDGF-AB and PDGF-BB was enhanced. These results define a role for the PDGFR-alpha as a regulatory receptor subtype that is necessary for PDGF isoforms to exert maximal chemotaxis. |
| Databáze: | OpenAIRE |
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