Environmental and developmental effects on alveolar macrophages in normal children

The lung is constantly exposed to respirable biological as well as inorganic particles. Alveolar macrophages (AM) are crucial to our immunological response to these, directly via their phagocytic abilities and indirectly through their interactions with other cells. AM are immature in both morphology and function in early life. Two key features of AM potentially important for pulmonary disease in childhood are first their interaction with particulates, and second their effects on T cell mediated immune activation in early life. Changes in these morphological and functional features may be critically important for the association between exposure to environmental air pollutants and respiratory disease in children, the increased susceptibility of the infant lung to viral respiratory infection, and the development of immunological tolerance. This thesis explores these hypotheses by first evaluating the laser scanning cytometer (LSC) as a means of studying AM phenotype using the pan-macrophage marker CD68; second examining developmental and natural in vivo exposure effects on particle loading of AM and expression of the receptor which mediates uptake of unopsonized particles, the macrophage receptor with collagenous structure (MARCO); and third studying developmental changes in the effects of AM on mitogen stimulated autologous peripheral blood mononuclear cell (PBMC) proliferation, and the mechanisms underlying any differences.