Negative regulatory role of mannose receptors on human alveolar macrophage proinflammatory cytokine release in vitro

Alveolar macrophages (AM) are critical components of lung innate immunity and contribute to an effective host response to Pneumocystis pneumonia. Recognition of unopsonized Pneumocystis organisms by human AM is mediated predominantly via mannose receptors and results in phagocytosis, release of reac...

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Published in:Journal of leukocyte biology 2005-09, Vol.78 (3), p.665-674
Main Authors: Zhang, Jianmin, Tachado, Souvenir D., Patel, Naimish, Zhu, Jinping, Imrich, Amy, Manfruelli, Pascal, Cushion, Melanie, Kinane, T. Bernard, Koziel, Henry
Format: Article
Language:English
Subjects:
Adolescent
Adult
Animals
Cytokines - biosynthesis
Feedback, Physiological - immunology
Female
Gene Silencing
host defense
Humans
immunology
In Vitro Techniques
innate immunity
Interleukin-8 - biosynthesis
Interleukin-8 - immunology
Lectins, C-Type - genetics
Lectins, C-Type - immunology
Lipopolysaccharides - pharmacology
Macrophages, Alveolar - drug effects
Macrophages, Alveolar - immunology
Macrophages, Alveolar - microbiology
Male
Mannose-Binding Lectins - genetics
Mannose-Binding Lectins - immunology
Matrix Metalloproteinase 9 - biosynthesis
Matrix Metalloproteinase 9 - immunology
Middle Aged
NF-kappa B - immunology
phagocytosis
Pneumocystis
Pneumocystis - immunology
Pulmonary Alveoli - immunology
Rats
Rats, Inbred Lew
Rats, Inbred Strains
Receptors, Cell Surface - genetics
Receptors, Cell Surface - immunology
Reference Values
Tumor Necrosis Factor-alpha - biosynthesis
Tumor Necrosis Factor-alpha - drug effects
Tumor Necrosis Factor-alpha - immunology
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Summary:Alveolar macrophages (AM) are critical components of lung innate immunity and contribute to an effective host response to Pneumocystis pneumonia. Recognition of unopsonized Pneumocystis organisms by human AM is mediated predominantly via mannose receptors and results in phagocytosis, release of reactive oxygen species, and activation of the nuclear transcription factor (NF)‐κB. However, the AM host defense genes activated by Pneumocystis have not been defined. In the present study, incubation of AM with unopsonized Pneumocystis organisms was not associated with release of interleukin (IL)‐1β, IL‐6, or tumor necrosis factor (TNF)‐α (important cytokines in the host response to Pneumocystis) and did not induce IL‐1β, IL‐6, or TNF‐α mRNA transcripts. These findings were not attributed to Pneumocystis‐induced cytopathic changes, as these same AM released IL‐8 and matrix metalloproteinase‐9 in response to Pneumocystis. NF‐κB‐mediated IL‐8 release was independent of Pneumocystis phagocytosis. The observed response was specific, as IL‐1β, IL‐6, and TNF‐α release and mRNA induction were preserved in response to lipopolysaccharide or serum‐opsonized Pneumocystis. The absence of IL‐1β, IL‐6, and TNF‐α release in response to Pneumocystis was predominately influenced by AM mannose receptors, as blocking mannose receptors or targeted mannose receptor small interfering RNA functional gene silencing resulted in TNF‐α release in response to unopsonized Pneumocystis organisms. Furthermore, ligation of AM mannose receptors by unopsonized Pneumocystis organisms reduced Toll‐like receptor 4‐mediated TNF‐α release. Taken together, these data suggest that mannose receptors on human AM may suppress select proinflammatory cytokine release and may serve to regulate the innate inflammatory responses to infectious challenge in the lungs.
ISSN:0741-5400
1938-3673
DOI:10.1189/jlb.1204699