Selective activation of human intestinal mast cells by Escherichia coli hemolysin.
Mast cells (MCs) are recognized to play an important role in bacterial host defense in the murine system. In this study, we studied the interaction of human MCs, isolated from the intestine and purified to homogeneity, with different Escherichia coli and Shigella flexneri strains. We show that alpha-hemolysin (Hly)-producing E. coli strains induce the release of histamine, leukotrienes, and proinflammatory cytokines in intestinal MCs. In contrast, MCs were virtually unresponsive to S. flexneri and several Hly-negative E. coli strains, including the isogenic Hly-deficient mutants of Hly(+) strains. Hly(+) E. coli but not Hly(-) E. coli caused an increase in intracellular Ca(2+) levels. Blocking of extracellular Ca(2+) and of the calmodulin/calcineurin pathway by cyclosporin A inhibited the response to Hly(+) E. coli. Furthermore, inhibition of MAPKs p38 and ERK reduces activation of MCs by Hly(+) E. coli. In addition, using an ex vivo system, we directly record the histamine release by MCs located in the lamina propria after infection with Hly(+) E. coli. Our data indicate that human intestinal mast cells interact with selected Gram-negative bacteria, establish E. coli Hly as a factor regulating MC effector functions, and argue further for a role of human MCs in innate immunity.
Krämer
Sigrid
S
Department of Nutritional Medicine and Immunology, University of Hohenheim, Stuttgart, Germany.
Sellge
Gernot
G
Lorentz
Axel
A
Krueger
Dagmar
D
Schemann
Michael
M
Feilhauer
Katharina
K
Gunzer
Florian
F
Bischoff
Stephan C
SC
D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004926:Escherichia coli / Q000276:immunology*; D029968:Escherichia coli Proteins / Q000276:immunology / Q000378:metabolism; D006460:Hemolysin Proteins / Q000276:immunology* / Q000378:metabolism; D006636:Histamine Release; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D015289:Leukotrienes / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*
D016207:Cytokines; D029968:Escherichia coli Proteins; D006460:Hemolysin Proteins; D018836:Inflammation Mediators; D015289:Leukotrienes; D020929:Mitogen-Activated Protein Kinase Kinases; D002118:Calcium