Pseudomonas aeruginosa-induced human mast cell apoptosis is associated with up-regulation of endogenous Bcl-xS and down-regulation of Bcl-xL.
Mast cells play a critical role in the host defense against bacterial infection. Recently, apoptosis has been demonstrated to be essential in the regulation of host response to Pseudomonas aeruginosa. In this study we show that human mast cell line HMC-1 and human cord blood-derived mast cells undergo apoptosis as determined by the ssDNA formation after infection with P. aeruginosa. P. aeruginosa induced activation of caspase-3 in mast cells as evidenced by the cleavage of D4-GDI, an endogenous caspase-3 substrate and the generation of an active form of caspase-3. Interestingly, P. aeruginosa treatment induced up-regulation of Bcl-x(S) and down-regulation of Bcl-x(L). Bcl-x(S), and Bcl-x(L) are alternative variants produced from the same Bcl-x pre-mRNA. The former is proapoptotic and the latter is antiapoptotic likely through regulating mitochondrial membrane integrity. Treatment of mast cells with P. aeruginosa induced release of cytochrome c from mitochondria and loss of mitochondrial membrane potentials. Moreover, P. aeruginosa treatment reduced levels of Fas-associated death domain protein-like IL-1beta-converting enzyme-inhibitory proteins (FLIPs) that are endogenous apoptosis inhibitors through counteraction with caspase-8. Thus, human mast cells undergo apoptosis after encountering P. aeruginosa through a mechanism that likely involves both the Bcl family protein mitochondrial-dependent and the FLIP-associated caspase-8 pathways.
Jenkins
Christopher E
CE
Department of Microbiology and Immunology and Department of Pediatrics, Dalhousie University, 5850 University Avenue, Halifax, Nova Scotia, Canada.
Swiatoniowski
Ania
A
Power
Melanie R
MR
Lin
Tong-Jun
TJ
D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D015536:Down-Regulation; D005434:Flow Cytometry; D006801:Humans; D008407:Mast Cells / Q000382:microbiology* / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism; D011552:Pseudomonas Infections / Q000378:metabolism*; D011550:Pseudomonas aeruginosa; D015854:Up-Regulation; D051020:bcl-X Protein / Q000378:metabolism*
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D051020:bcl-X Protein; D045304:Cytochromes c; D053148:Caspase 3