Abstract
Inspired air contains a myriad of potential pathogens, pollutants and inflammatory stimuli. In the normal lung, these pathogens are rarely problematic. This is because the epithelial lining fluid in the lung is rich in many innate immunity proteins and peptides that provide a powerful anti-microbial screen. These defensive proteins have anti-bacterial, anti- viral and in some cases, even anti-fungal properties. Their antimicrobial effects are as diverse as inhibition of biofilm formation and prevention of viral replication. The innate immunity proteins and peptides also play key immunomodulatory roles. They are involved in many key processes such as opsonisation facilitating phagocytosis of bacteria and viruses by macrophages and monocytes. They act as important mediators in inflammatory pathways and are capable of binding bacterial endotoxins and CPG motifs. They can also influence expression of adhesion molecules as well as acting as powerful anti-oxidants and anti-proteases. Exciting new antimicrobial and immunomodulatory functions are being elucidated for existing proteins that were previously thought to be of lesser importance. The potential therapeutic applications of these proteins and peptides in combating infection and preventing inflammation are the subject of ongoing research that holds much promise for the future.
Highlights
The host response to bacterial infection of the airways is dependent on both innate and adaptive immune systems
We have shown previously that lactoferrin levels are depleted in bronchoalveolar lavage (BAL) from Cystic Fibrosis patients with active Pseudomonas infections compared to those with no active Pseudomonas infection and that this depletion results in impaired ability to prevent Pseudomonas biofilm formation [25]
It is stored in neutrophil primary granules and exerts its effects through three distinct mechanisms: firstly, it is directly cytotoxic via its effects on bacterial membranes; secondly, it acts as an opsonin to enhance neutrophil phagocytosis and thirdly, it can neutralise bacterial LPS [75]
Summary
The host response to bacterial infection of the airways is dependent on both innate (non-antibody-mediated) and adaptive (antibody-mediated) immune systems. (vi) Bactericidal Permeability-Increasing protein (BPI) BPI is a 55-kDa protein that is predominantly active against Gram-negative bacteria [2,74] It is stored in neutrophil primary granules and exerts its effects through three distinct mechanisms: firstly, it is directly cytotoxic via its effects on bacterial membranes; secondly, it acts as an opsonin to enhance neutrophil phagocytosis and thirdly, it can neutralise bacterial LPS [75]. Perhaps the ideal combination would be a nebulised innate immunity protein (eg lactoferrin) to augment depleted natural levels coupled with a synthetic cathepsin inhibitor to prevent proteolytic degradation Implementation of such a regime early in CF before biofilms have taken hold could potentially reduce morbidity and mortality from P. aeruginosa infections in CF significantly. Synergistic combinations of innate immunity proteins with existing antibacterial and antifungal agents should continue to be evaluated [102]
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