Innate Host Defense of the Airspaces
Over the course of a single day, millions of micro-organisms are inhaled providing the potential for colonization of the airspaces, epithelial cell injury and, ultimately, disruption of gas exchange. Inhaled micro-organisms are rapidly eliminated from the airspaces by antimicrobial proteins/peptides that directly kill or facilitate phagocytosis of micro-organisms by alveolar macrophages. The goal of research in the Weaver lab is to identify antimicrobial peptides/pathways that provide the first line of defense against inhaled micro-organisms.
Current projects are directed toward identification of:
- The molecular mechanism(s) underlying the bactericidal properties of lysozyme and surfactant protein B;
- Genetic program(s) that regulate expression of host defense peptides in the developing lung;
- Novel antimicrobial peptides for treatment of antibiotic resistant respiratory pathogens.
 Click to enlarge.
The first line of defense against inhaled micro-organisms is comprised of antimicrobial peptides that are constitutively secreted into the airspaces where they directly kill microbes. Other components of innate host defense include phagocytic cells (macrophages), antimicrobial peptides that are induced in response to infection and proteins that facilitate uptake of pathogens by macrophages. |  Click to enlarge .
Live bacteria (panels A-C) stain green whereas dead bacteria stain red (panels D-F). Treatment of bacteria with surfactant protein B (SP-B) results in extensive aggregation and killing of bacteria (panels G-L). |
Related Publications
Ryan, MA, Akinbi, HT, Serrano, AG, Perez-Gil, J, Wu, H, McCormack, FX and Weaver, TE: Antimicrobial activity of native and synthetic surfactant protein B peptides. Journal of Immunology, in press.
Markart, P, Korfhagen, TR, Weaver, TE and Akinbi, HT: Mouse lysozyme M is important in pulmonary host defense against Klebsiella pneumoniae infection. American Journal of Respiratory and Critical Care Medicine 169:454-458, 2004.
Markart, P, Faust, N, Graf, T, Na, C-L, Weaver, TE and Akinbi,\ HT: Comparison of the microbicidal and muramidase activities of mouse lysozyme M and P. Biochemical Journal 380:385-392, 2004.
