Airway macrophages in health and disease

Published on October 7, 2014   35 min

Other Talks in the Series: Macrophage Heterogeneity and Function

0:00
Hello. My name is Tracy Hussell. I am currently the Director of the Manchester Collaborative Centre for Inflammation Research. I'm also a professor of inflammatory disease at the University of Manchester in the United Kingdom. My email address is shown at the bottom of this slide should you want to speak with me. And today I'm going to talk about airway macrophages in health and disease.
0:32
My group has been working for a number of years now on the regulation of airway macrophages in health, how that regulation is lost during an inflammatory condition, and the altered state that it ends up in upon inflammatory resolution. And we believe that all of these changes are dictated by the respiratory epithelium. So the respiratory epithelium, when it is intact, provides a number of negative regulatory signals that raise the threshold above which an airway macrophage will become activated. So, for example, the respiratory epithelium secretes surfactant proteins, shown by the red and yellow star, which will bind to receptors such as the one shown here, SIRP alpha. And that transmits a negative regulatory signal to the airway macrophage. The respiratory epithelium can also activate transforming growth factor beta via the expression of that beta six integrins. And this combination also provides a negative regulatory signal to airway macrophages. Mucins secreted and expressed on the luminal aspect of the respiratory epithelium are also immune-suppressive, as is the expression of high levels of the immunoglobulin receptor CD200 that binds to CD200 receptors on airway macrophages. So as you can see from this slide, there are a number of things provided by or expressed by the respiratory epithelium that raise the threshold above which an airway macrophage can become activated. Now, it's likely that polymorphisms exist in all of these things that I've shown you here, which means that we will all have a slightly different state above which our airway macrophages will become activated. We feel that these concepts are relevant to multiple inflammatory conditions, and it gives us a different concept, in a way, in that it's not just antigen that drives an inflammatory response, it's an antigen that is sufficient enough to disrupt the respiratory epithelium. So for inflammation to proceed in the respiratory tract, we need an antigen and we also need a loss of epithelium, which will take away the regulation that normally controls airway macrophages. All of the concepts that I'm dealing with are relevant to all of these following conditions: asthma, COPD, idiopathic pulmonary fibrosis, cystic fibrosis, lung cancer, bronchitis, bronchiectasis, pneumonia, and infection. And this concept is what I'm going to talk about in the rest off my lecture today.
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Airway macrophages in health and disease

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