Relationship between antimicrobial proteins and airway inflammation and infection in cystic fibrosis

Abstract

Antimicrobial proteins are important in lung defense and are potential therapeutic agents in chronic airways infection such as seen in cystic fibrosis (CF). In preparation for future clinical studies, we sought (1) to determine levels of three antimicrobial proteins [lactoferrin, lysozyme, and secretory leukoprotease inhibitor (SLPI)] in the CF airway and (2) to examine the relationships between these antimicrobial proteins and airway inflammation and infection. We examined bronchoalveolar lavage fluid (BALF) from 45 individuals with CF and 23 disease control individuals. Airway inflammation was measured through BALF neutrophil counts and neutrophil elastase activity. Infection was assessed through quantitative counts of CF-related bacterial pathogens. BALF lysozyme activity and lactoferrin levels were elevated in individuals with CF compared to controls whereas SLPI levels were not different between the groups. Among the CF subjects, lysozyme activity and lactoferrin increased with age while SLPI decreased with age. Lysozyme activity and lactoferrin concentrations correlated positively with neutrophil counts but not with bacterial colony counts. SLPI levels were inversely related to both neutrophil counts and bacterial colony counts. This study provides information concerning the levels of antimicrobial proteins present in the CF airway that are relevant to future clinical trials of these compounds and demonstrates clear relationships between antimicrobial protein-specific levels and airway inflammation and infection.

Exposure to Swine Housing Dust Modulates Macrophage Morphology and Function

“…There was also a trend of higher BALF protein levels in mice that inhaled 5 and 25% DE than inhalation of PBS, although these values did not reach formal significance (p<0.05). Measurement of BALF components including immune cells, microbial/host protein content, cytokines and chemokines, is the method of choice for elevating airway and lung inflammation (Elizur et al, 2008;Sagel et al, 2009). This is consistent with findings reported by Poole et al (2007) where acute exposure to dust induces an inflammatory response demonstrated by secretion of proinflammatory cytokines; however, re-stimulation resulted in a diminished response.…”

SPLUNC1 Promotes Lung Innate Defense Against Mycoplasma pneumoniae Infection in Mice

“…[27][28][29] In addition, airway epithelial cells produce several other major host defense molecules such as lactotransferrin. 30 The present results of impaired Mp clearance from SPLUNC1 Ϫ/Ϫ mouse lungs advance the lung innate immunity field by demonstrating the in vivo function of SPLUNC1. Furthermore, it was demonstrated that hSPLUNC1 inhibited Mp growth, thus extending previous results using mouse SPLUNC1 protein.…”

EnhancedIn VitroFormation and Antibiotic Resistance of Nonattached Pseudomonas aeruginosa Aggregates through Incorporation of Neutrophil Products

“…Instead, P. aeruginosa growth in the CF airway occurs in the context of stagnant mucous plugs, which are lodged in the airway lumen (6,11). The exuberance of the immune response results in excessive neutrophil accumulation that can overwhelm the capacity of the host to clear neutrophils from the tissue, resulting in sputum that is highly enriched in neutrophil-derived products implicated in CF lung pathogenesis (1,(14)(15)(16)(17)(18)(19). Neutrophil survival in this setting is limited to just a few hours as a consequence of apoptosis and necrosis (20,21).…”