Am. J. Respir. Cell Mol. Biol., Volume 19, Number 6, December, 1998 920-928

Effects of Ion Composition and Tonicity on Human Neutrophil Antibacterial Activity

Margrith W. Verghese and Richard C. Boucher

Cystic Fibrosis/Pulmonary Research and Treatment Center, Division of Pulmonary Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

Infants with cystic fibrosis (CF) often are infected with Staphylococcus aureus (S. aur.), which is followed by colonization with Pseudomonas aeruginosa (P. aerug.). In spite of an excessive, neutrophil-dominated inflammatory response in the respiratory tract, patients with CF often succumb to pulmonary infections with P. aerug. Because peripheral blood neutrophils of these patients have normal functions, we examined whether hypothesized alterations of the airway surface liquids (ASL) in these patients significantly impair neutrophil bactericidal activity in the microenvironment of the CF lung. The ionic composition of CF ASL is still not entirely defined and has been speculated to be abnormally high or abnormally low in Na⁺ and Cl concentrations; estimates of osmolarities have ranged from 200 (hypo-osmolar) to 285 (iso-osmolar) to > 300 meq/L (hyper-osmolar). Our data indicate that bacterial killing activity of human peripheral blood neutrophils against P. aerug. or S. aur. is not decreased in buffers in which NaCl was replaced with equimolar concentrations of choline Cl, KCl, or N-methyl-D-glucamine chloride to maintain isotonicity. Amiloride or benzamil, known modulators of Na⁺ transport in neutrophils, did not interfere with this neutrophil function. Deviations from isotonicity of ± 50% also failed to diminish bactericidal activity of neutrophils significantly. In contrast, superoxide production and enzyme secretion in response to the chemotactic peptide N-formylmethionylleucylphenylalanine appeared to be sensitive to the ionic milieu of the assay buffers. Our results suggest that the postulated alterations in the ionic composition of ASL in CF lungs are insufficient to explain why neutrophils fail to clear infections with P. aerug. in these patients.

This article has been cited by other articles:

				T. J. Moraes, J. Plumb, R. Martin, E. Vachon, V. Cherepanov, A. Koh, C. Loeve, J. Jongstra-Bilen, J. H. Zurawska, J. V. Kus, et al. Abnormalities in the Pulmonary Innate Immune System in Cystic Fibrosis Am. J. Respir. Cell Mol. Biol., March 1, 2006; 34(3): 364 - 374. [Abstract] [Full Text] [PDF]

				H. Matsui, M. W. Verghese, M. Kesimer, U. E. Schwab, S. H. Randell, J. K. Sheehan, B. R. Grubb, and R. C. Boucher Reduced Three-Dimensional Motility in Dehydrated Airway Mucus Prevents Neutrophil Capture and Killing Bacteria on Airway Epithelial Surfaces J. Immunol., July 15, 2005; 175(2): 1090 - 1099. [Abstract] [Full Text] [PDF]

				K. R. Khubchandani, R. E. Oberley, and J. M. Snyder Effects of Surfactant Protein A and NaCl Concentration on the Uptake of Pseudomonas aeruginosa by THP-1 Cells Am. J. Respir. Cell Mol. Biol., December 1, 2001; 25(6): 699 - 706. [Abstract] [Full Text] [PDF]