Molecular composition of the alveolar lining fluid in the aging lung
As we age, there is an increased risk for the development of pulmonary diseases, including infections, but few studies have considered changes in lung surfactant and components of the innate immune system as contributing factors to the increased susceptibility of the elderly to succumb to infections. We and others have demonstrated that human alveolar lining fluid (ALF) components, such as surfactant protein (SP)-A, SP-D, complement protein C3, and alveolar hydrolases, play a significant innate immune role in controlling microbial infections. However, there is a lack of information regarding the effect of increasing age on the level and function of ALF components in the lung. Here we addressed this gap in knowledge by determining the levels of ALF components in the aging lung that are important in controlling infection. Our findings demonstrate that pro-inflammatory cytokines, surfactant proteins and lipids, and complement components are significantly altered in the aged lung in both mice and humans. Further, we show that the aging lung is a relatively oxidized environment. Our study provides new information on how the pulmonary environment in old age can potentially modify mucosal immune responses, thereby impacting pulmonary infections and other pulmonary diseases in the elderly population.
KeywordsInflammation Aging Alveolar lining fluid Surfactant Complement
This work was supported by a The Ohio State University Public Health Preparedness for Infectious Diseases (PHPID) pilot award to JT, JBT, LSS, WL, SW, J(X)P, and PR Jr, and a Julie Martin Mid-Career American Federation of Aging Research (AFAR) award to JT, and partially by a NIH/NIAD R01 [AI-093570] to JBT. JIM was partially supported by a NIH/NIGMS T32-GM068412. We thank Dr. Patsy Skabla for assisting with patient enrollment. We also thank the Campus Chemical Instrument Center (CCIC) at The Ohio State University for their services.
- Carlson TK, Brooks M, Meyer D, Henning L, Murugesan V et al (2010) Pulmonary innnate immunity: soluble and cellular host defenses of the lung. In: Marsh C, Tridandapani S, Piper M (eds) Regulation of innate immune function. Transworld Research Network, Kerala, pp 165–211Google Scholar
- Gupta GS, Gupta A, Gupta RK (2012) Animal lectins: form, functions and clinical applications. Springer, LondonGoogle Scholar
- Notter RH (2000) Lung surfactants: basic science and clinical applications. Marcel Dekker, New York, pp 1–444Google Scholar
- Postle AD (2008) Phospholipid profiling. In: Griffiths W (ed) Metabolomics, metabonomics, and metabolite profiling. The Royal Society of Chemistry, Cambridge, pp 116–133Google Scholar
- Retini C, Kozel TR, Pietrella D, Monari C, Bistoni F, Vecchiarelli A (2001) Interdependency of interleukin-10 and interleukin-12 in regulation of T-cell differentiation and effector function of monocytes in response to stimulation with Cryptococcus neoformans. Infect Immun 69:6064–6073PubMedCrossRefPubMedCentralGoogle Scholar
- Torrelles JB (2012) Broadening our view about the role of Mycobacterium tuberculosis cell envelope components during infection: a battle for survival. In: Cardona PJ (ed) Understanding tuberculosis—analyzing the origin of Mycobacterium tuberculosis pathogenicity. Intech, Rijeka, pp 1–46Google Scholar
- Young SL, Fram EK, Larson E, Wright JR (1993) Recycling of surfactant lipid and apoprotein-A studied by electron microscopic autoradiography. Am J Physiol Lung Cell Mol Physiol 265:L19–L26Google Scholar