title: Intestinal macrophages lack CD14 and CD89 and consequently are down-regulated for LPS- and IgA-mediated activities.
abstract: The intestinal mucosa normally displays minimal inflammation despite the close proximity between mucosal macrophages and lumenal bacteria. Macrophages interact with bacteria and their products through CD14, a surface receptor involved in the response to LPS, and CD89, the receptor for IgA (FcalphaR). Here we show that resident macrophages isolated from normal human intestine lack CD14 and CD89. The absence of CD14 and CD89 was not due to the isolation procedure or mucosal cell products, but was evident at the transcriptional level, as the macrophages expressed neither CD14- nor CD89-specific mRNAs, but did express Toll-like receptor 2 and 4 transcripts. Consistent with their CD14(-) phenotype, lamina propria macrophages displayed markedly reduced LPS-induced cytokine production and LPS-enhanced phagocytosis. In addition, IgA-enhanced phagocytosis was sharply reduced in lamina propria macrophages. Thus, the absence of CD14 and CD89 on resident intestinal macrophages, due to down-regulated gene transcription, causes down-modulated LPS- and IgA-mediated functions and probably contributes to the low level of inflammation in normal human intestinal mucosa.
authors.affiliation: Department of Medicine, University of Alabama, and Veterans Affairs Medical Center, Birmingham, AL 35294, USA. pdsmith@uab.edu
authors.forename: P D
authors.initials: PD
authors.lastname: Smith
authors.forename: L E
authors.initials: LE
authors.lastname: Smythies
authors.forename: M
authors.initials: M
authors.lastname: Mosteller-Barnum
authors.forename: D A
authors.initials: DA
authors.lastname: Sibley
authors.forename: M W
authors.initials: MW
authors.lastname: Russell
authors.forename: M
authors.initials: M
authors.lastname: Merger
authors.forename: M T
authors.initials: MT
authors.lastname: Sellers
authors.forename: J M
authors.initials: JM
authors.lastname: Orenstein
authors.forename: T
authors.initials: T
authors.lastname: Shimada
authors.forename: M F
authors.initials: MF
authors.lastname: Graham
authors.forename: H
authors.initials: H
authors.lastname: Kubagawa
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D016207:Cytokines / Q000096:biosynthesis; D017931:DNA Primers / Q000235:genetics; D015536:Down-Regulation; D029721:Drosophila Proteins; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000166:cytology* / Q000276:immunology*; D007583:Jejunum / Q000166:cytology / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D017931:DNA Primers; D029721:Drosophila Proteins; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011961:Receptors, Fc; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors