The increase in ASMC mass is a major structural change described in airway remodeling in asthma. This increase has been attributed to ASMC hyperplasia and hypertrophy. The distance between ASMC and the epithelium is reduced suggesting expansion of the muscle bundle towards the epithelium. Recent studies have suggested a role of epithelial derived chemokines in ASMC migration toward the epithelium. We hypothesized that chemokines (Eotaxin, RANTES, MIP-1alpha and IL-8) can directly influence ASMC mass by increasing the rate of proliferation or enhancing survival. ASMCs were exposed to different concentrations of eotaxin, RANTES, IL-8 or MIP-1alpha. To test for proliferation, stimulated ASMC were pulsed with 3H-thymidine or stained with BrdU and then analyzed with flow cytometry. Apoptosis was measured using Annexin V and flow cytometry. Expression of phosphorylated p42/p44 and MAPKinases was assessed by Western analysis. In a concentration-dependent manner, chemokines such as Eotaxin, RANTES, IL-8 and MIP-lalpha increased ASMCs 3H-thymidine incorporation and DNA synthesis. Eotaxin, RANTES and IL-8 decreased the number of apoptotic ASMCs compared to the matched controls. A significant increase in phosphorylated p42/p44 MAPKs was seen after treating ASMCs with RANTES and eotaxin. We conclude that chemokines might contribute to airway remodeling by increasing the number of ASMCs.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.112369 |
| Date | January 2008 |
| Creators | Al Abri, Jehan. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Pathology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002826154, proquestno: AAIMR51058, Theses scanned by UMI/ProQuest. |
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