Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2013 (2013), Article ID 742184, 13 pages
Research Article

Low pH Environmental Stress Inhibits LPS and LTA-Stimulated Proinflammatory Cytokine Production in Rat Alveolar Macrophages

1Department of Medicine, Division of Cardiovascular Medicine, University at Buffalo, Suite 7030, 875 Ellicott Street, Buffalo, NY 14203, USA
2Department of Anesthesiology, University at Buffalo, 3435 Main Street, Buffalo, NY 14214, USA
3Department of Microbiology, University at Buffalo, 3435 Main Street, Buffalo, NY 14214, USA

Received 3 May 2013; Revised 12 July 2013; Accepted 17 July 2013

Academic Editor: Carlo Jose Freire de Oliveira

Copyright © 2013 Stanley F. Fernandez et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Gastric aspiration increases the risks for developing secondary bacterial pneumonia. Cytokine elaboration through pathogen recognition receptors (PRRs) is an important mechanism in initiating innate immune host response. Effects of low pH stress, a critical component of aspiration pathogenesis, on the PRR pathways were examined, specifically toll-like receptor-2 (TLR2) and TLR4, using isolated rat alveolar macrophages (aMØs). We assessed the ability of aMØs after brief exposure to acidified saline to elaborate proinflammatory cytokines in response to lipopolysaccharide (LPS) and lipoteichoic acid (LTA) stimulation, known ligands of TLR4 and TLR2, respectively. Low pH stress reduced LPS- and LTA-mediated cytokine release (CINC-1, MIP-2, TNF- , MCP-1, and IFN- ). LPS and LTA increased intracellular Ca2+ concentrations while Ca2+ chelation by BAPTA decreased LPS- and LTA-mediated cytokine responses. BAPTA blocked the effects of low pH stress on most of LPS-stimulated cytokines but not of LTA-stimulated responses. In vivo mouse model demonstrates suppressed E. coli and S. pneumoniae clearance following acid aspiration. In conclusion, low pH stress inhibits antibacterial cytokine response of aMØs due to impaired TLR2 (MyD88 pathway) and TLR4 signaling (MyD88 and TRIF pathways). The role of Ca2+ in low pH stress-induced signaling is complex but appears to be distinct between LPS- and LTA-mediated responses.