title: Impaired neonatal macrophage phagocytosis is not explained by overproduction of prostaglandin E2.
abstract: BACKGROUND
  Neonates and young infants manifest increased susceptibility to bacterial, viral and fungal lung infections. Previous work has identified a role for eicosanoids in mediating host defense functions of macrophages. This study examines the relationship between alveolar macrophage (AM) host defense and production of lipid mediators during the neonatal period compared to adult AMs.
  
  
  METHODS
  AMs were harvested from young (day 7 and day 14) and adult (~10 week) rats. The functionality of these cells was assessed by examining their ability to phagocytose opsonized targets, produce cytokines, eicosanoids and intracellular cAMP measured by enzyme immunoassays, and gene expression of proteins, enzymes and receptors essential for eicosanoid generation and phagocytosis measured by real time RT-PCR.
  
  
  RESULTS
  AMs from young animals (day 7 and 14) were defective in their ability to phagocytose opsonized targets and produce tumor necrosis factor (TNF)- α. In addition, young AMs produce more prostaglandin (PG) E(2), a suppressor of host defense, and less leukotriene (LT) B(4), a promoter of host defense. Young AMs express higher levels of enzymes responsible for the production of PGE(2) and LTB(4); however, there was no change in the expression of E prostanoid (EP) receptors or LT receptors. Despite the similar EP profiles, young AMs are more responsive to PGE(2) as evidenced by their increased production of the important second messenger, cyclic AMP. In addition, young AMs express higher levels of PDE3B and lower levels of PDE4C compared to adult AMs. However, even though the young AMs produced a skewed eicosanoid profile, neither the inhibition of PGE(2) by aspirin nor the addition of exogenous LTB(4) rescued the defective opsonized phagocytosis. Examination of a receptor responsible for mediating opsonized phagocytosis showed a significant decrease in the gene expression levels of the Fcgamma receptor in young (day 7) AMs compared to adult AMs.
  
  
  CONCLUSIONS
  These results suggest that elevated production of PGE(2) and decreased production of LTB(4) do not contribute to impaired opsonized macrophage phagocytosis and highlight an important difference between young and adult AMs.
authors.affiliation: Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, The University of Michigan, Ann Arbor, MI, USA. mnhender@umich.edu
authors.forename: Megan N
authors.initials: MN
authors.lastname: Ballinger
authors.forename: Marc
authors.initials: M
authors.lastname: Peters-Golden
authors.forename: Bethany B
authors.initials: BB
authors.lastname: Moore
mesh_terms: D000367:Age Factors; D000375:Aging / Q000276:immunology; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D007124:Immunoenzyme Techniques; D018836:Inflammation Mediators / Q000378:metabolism*; D007975:Leukotriene B4 / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D018055:Receptors, Eicosanoid / Q000235:genetics / Q000378:metabolism; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger; D018055:Receptors, Eicosanoid; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D007975:Leukotriene B4; D000242:Cyclic AMP; D015232:Dinoprostone