**6.5 Age-associated change in alveolar macrophage abundance**

A previous study reported a significantly reduced proportion of alveolar macrophages in bronchoalveolar lavage fluid cells in the elderly [115]. Likewise, aged mice indicated decreased numbers of alveolar macrophages per unit lung weight in two strains (BALB/c and C57BL/6 J), which was accompanied by the downregulation of gene expression that regulates the cell cycle [93]. These findings suggest that the quantitative decline in alveolar macrophages with age partially contributes to the high vulnerability to acute LRTIs in the elderly. In another recent study, the gene expression profile was reproduced in murine as well as human alveolar macrophages; however, this property could be mediated by the inhibition of GM-CSF signaling in alveolar macrophages due to age-dependent alterations in the alveolar microenvironment (especially, increased hyaluronan levels in the alveolar epithelial lining fluid), but not due to cell-autonomous mechanisms such as alterations in intracellular

*Physiological Role of Alveolar Macrophage in Acute Lower Respiratory Tract Infection… DOI: http://dx.doi.org/10.5772/intechopen.110509*

signaling protein levels or circulating monocyte migration [114]. Indeed, the transplantation of alveolar macrophages from aged mice into the alveoli of young mice reverted age-related changes in the transcriptome to a state resembling young alveolar macrophages [114]. Although the importance of age-associated changes in the tissue microenvironment has long been proposed [21], recent advances in research methods and techniques have made it possible to elucidate the role of age-related alterations in the alveolar microenvironment. Therefore, the mechanism by which aging reduces phagocytosis, pro-inflammatory responses, and efferocytosis can be primarily explained by the inhibition of the differentiation or maturation of alveolar macrophages through microenvironmental degeneration.
