title: Ontogeny of rat pulmonary alveolar macrophage function: evidence for a selective deficiency in il-10 and nitric oxide production by newborn alveolar macrophages.
abstract: Alveolar macrophages (AM) play a crucial role in host defence by secretion of a large repertoire of biological response modifiers (BRM) following challenge. Newborns manifest increased susceptibility to lung infections, suggesting a deficiency in AM-mediated host defence. Thus, we investigated the ontogeny of BRM production by resting and stimulated AM. We analysed the capacity of rat AM to produce mRNA specific for a range of cytokines including tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, IL-10, IL-12, IL-18, and the enzyme inducible nitric oxide synthase, in response to in vitro lipopolysaccharide (LPS) challenge. We report that production of nitric oxide by newborn AM under conditions of maximal stimulation was impaired. In addition, expression of IL-10 was only minimally upregulated in AM from newborns in response to LPS compared to adults. Inability to upregulate expression of IL-10 appeared to be influenced by microenvironmental factors, since peritoneal macrophages from newborns responded to LPS with significant upregulation of IL-10. Furthermore, when newborn AM were precultured in vitro, IL-10 responsiveness to LPS was partially restored. In contrast, cytokines such as TNF-alpha, IL-1, IL-6, IL-12 and IL-18 appeared to be expressed at adult levels by newborn AM. These results demonstrate that there may be functional differences in AM of newborns compared to adults, and these may be specific to the tissue compartment.
authors.affiliation: TVW Telethon Institute for Child Health Research, The University of Western Australia, Perth, Australia.
authors.forename: P T
authors.initials: PT
authors.lastname: Lee
authors.forename: P G
authors.initials: PG
authors.lastname: Holt
authors.forename: A S
authors.initials: AS
authors.lastname: McWilliam
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D007375:Interleukin-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007700:Kinetics; D008070:Lipopolysaccharides / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011650:Pulmonary Alveoli / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D007375:Interleukin-1; D020382:Interleukin-18; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat