Mannose-containing molecular patterns are strong inducers of cyclooxygenase-2 expression and prostaglandin E2 production in human macrophages.
The induction of cyclooxygenase-2 (COX-2) and the production of PGE(2) in response to pathogen-associated molecular patterns decorated with mannose moieties were studied in human monocytes and monocyte-derived macrophages (MDM). Saccharomyces cerevisiae mannan was a robust agonist, suggesting the involvement of the mannose receptor (MR). MR expression increased along the macrophage differentiation route, as judged from both its surface display assessed by flow cytometry and the ability of MDM to ingest mannosylated BSA. Treatment with mannose-BSA, a weak agonist of the MR containing a lower ratio of attached sugar compared with pure polysaccharides, before the addition of mannan inhibited COX-2 expression, whereas this was not observed when agonists other than mannan and zymosan were used. HeLa cells, which were found to express MR mRNA, showed a significant induction of COX-2 expression upon mannan challenge. Conversely, mannan did not induce COX-2 expression in HEK293 cells, which express the mRNA encoding Endo180, a parent receptor pertaining to the MR family, but not the MR itself. These data indicate that mannan is a strong inducer of COX-2 expression in human MDM, most likely by acting through the MR route. Because COX-2 products can be both proinflammatory and immunomodulatory, these results disclose a signaling route triggered by mannose-decorated pathogen-associated molecular patterns, which can be involved in both the response to pathogens and the maintenance of homeostasis.
Fernández
Nieves
N
Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas, Valladolid, Spain.
Alonso
Sara
S
Valera
Isela
I
Vigo
Ana González
AG
Renedo
Marta
M
Barbolla
Luz
L
Crespo
Mariano Sánchez
MS
D000936:Antigen-Antibody Complex / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis*; D004340:Drug Contamination; D005936:Glucans; D006367:HeLa Cells; D006801:Humans; D037181:Lectins, C-Type / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D008351:Mannans / Q000494:pharmacology; D008358:Mannose / Q000378:metabolism* / Q000502:physiology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D009000:Monocytes / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D011134:Polysaccharides / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology*; D051193:Toll-Like Receptors; D015054:Zymosan / Q000494:pharmacology; D000099181:Dectin-1
D000936:Antigen-Antibody Complex; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D005936:Glucans; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D008351:Mannans; D008358:Mannose; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011134:Polysaccharides; D011451:Prostaglandin-Endoperoxide Synthases; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D015054:Zymosan; D000099181:Dectin-1; C008247:laminaran; C496540:PTGS2 protein, human