Antimicrobial proteins and peptides in human lung diseases: A friend and foe partnership with host proteases.
Lung antimicrobial proteins and peptides (AMPs) are major sentinels of innate immunity by preventing microbial colonization and infection. Nevertheless bactericidal activity of AMPs against Gram-positive and Gram-negative bacteria is compromised in patients with chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF) and asthma. Evidence is accumulating that expression of harmful human serine proteases, matrix metalloproteases and cysteine cathepsins is markedely increased in these chronic lung diseases. The local imbalance between proteases and protease inhibitors compromises lung tissue integrity and function, by not only degrading extracellular matrix components, but also non-matrix proteins. Despite the fact that AMPs are somewhat resistant to proteolytic degradation, some human proteases cleave them efficiently and impair their antimicrobial potency. By contrast, certain AMPs may be effective as antiproteases. Host proteases participate in concert with bacterial proteases in the degradation of key innate immunity peptides/proteins and thus may play immunomodulatory activities during chronic lung diseases. In this context, the present review highlights the current knowledge and recent discoveries on the ability of host enzymes to interact with AMPs, providing a better understanding of the role of human proteases in innate host defense.
INSERM, UMR 1100, Pathologies Respiratoires: Protéolyse et Aérosolthérapie, Centre d'Etude des Pathologies Respiratoires, Equipe 2: « Mécanismes Protéolytiques dans l'Inflammation », Université François Rabelais, F-37032 Tours cedex, France. Electronic address: fabien.lecaille@univ-tours.fr.
Fabien
F
Lecaille
INSERM, UMR 1100, Pathologies Respiratoires: Protéolyse et Aérosolthérapie, Centre d'Etude des Pathologies Respiratoires, Equipe 2: « Mécanismes Protéolytiques dans l'Inflammation », Université François Rabelais, F-37032 Tours cedex, France.
Gilles
G
Lalmanach
INSERM, UMR 1100, Pathologies Respiratoires: Protéolyse et Aérosolthérapie, Centre d'Etude des Pathologies Respiratoires, Equipe 2: « Mécanismes Protéolytiques dans l'Inflammation », Université François Rabelais, F-37032 Tours cedex, France.
Pierre-Marie
PM
Andrault
D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008171:Lung Diseases / Q000378:metabolism* / Q000382:microbiology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D010447:Peptide Hydrolases
Antimicrobial peptides and proteins; Asthma; Chronic obstructive pulmonary disease; Cystic fibrosis; Inhibitors; Lung; Proteases