Rôle de l'axe SIRPa/CD47 dans l'inflammation pulmonaire induite par la fumée de cigarette

Authors: Routhier, Joanie
Advisor: Morissette, Mathieu
Abstract: RATIONAL. Smoking induces an inflammatory response in the lung that can cause significant tissue damage if sustained. Fortunately, there exist inflammatory regulatory pathways that help maintain and restore cellular homeostasis, such as through the signal regulatory protein alpha (SIRPa)/CD47 system. SIRPa is mainly expressed by myeloid cells while CD47 is found ubiquitously. It has been shown that activation of SIRPa by CD47-Fc fusion protein reduces the inflammatory pulmonary response in an ovalbumin-induced allergic asthma mouse model. Thus, we hypothesize that activation of SIRPa could limit lung inflammation induced by cigarette smoke exposure. OBJECTIVES. 1) To evaluate the effect of cigarette smoke on SIRPa mRNA and protein levels. 2) To investigate the impact of SIRPa activation on lung inflammatory response induced by cigarette smoke exposure. METHODS. SIRPa mRNA levels were explored by qPCR in BALB/c mice that were exposed to cigarette smoke 2 hours/day, 5 days/week during 2, 8 and 24 weeks. Also, 4 days cigarette smoke protocols were performed to investigate SIRPa protein levels by flow cytometry and to evaluate the impact of SIRPa activation by systemic administration of CD47-Fc. Treatment efficacy was determined via total and differential cellular count in the bronchoalveolar lavage (BAL). RESULTS. SIRPa mRNA levels were increased in the lungs of mice exposed to cigarette smoke. Although, the number of phagocytes expressing SIRPa protein seems to decrease, our data show that these cells expressed SIRPa at a higher intensity. Finally, we found that CD47-Fc treatment reduced neutrophilia in BAL of mice exposed to cigarette smoke. CONCLUSION. These results demonstrate that CD47-Fc treatment can reduce lung inflammation induced by cigarette smoke exposure, suggesting further research into CD47-Fc therapeutic potential is required.
Document Type: Mémoire de maîtrise
Issue Date: 2018
Open Access Date: 28 September 2018
Permalink: http://hdl.handle.net/20.500.11794/31470
Grantor: Université Laval
Collection:Thèses et mémoires

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