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Departments of Medicine (
*
Gastroenterology and
Developmental and Clinical Immunology),
Microbiology, and
Surgery and
¶ Pathology, University of Alabama, and
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Veterans Affairs Medical Center, Birmingham, AL 35294;
#
Department of Pathology, George Washington University School of Medicine, Washington, DC 20037; and
**
Department of Pediatrics, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298
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 (Fc
R). 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.
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