title: Change of annexin binding of monocytes as an expression of cellular response to Candida albicans: down-regulation in severe sepsis.
abstract: To study the differences of monocyte activation by albicans and non-albicans species of Candida and its change in sepsis, peripheral blood mononuclear cells were isolated from 17 healthy volunteers and 26 patients with severe sepsis/shock, and incubated in the absence/presence of heat-killed (HK) isolates of four different Candida species and purified β-D-glucan from C.albicans. Experiments were repeated in the presence and absence of inhibitors of intracellular activation pathways. Expression of annexin V on cells membranes of monocytes and lymphocytes, cytoplasmic activity of caspase-3, and DNA fragmentation of monocytes were studied. Membrane expression of annexin V on viable monocytes of healthy volunteers decreased significantly after incubation with C.albicans but not with non-albicans species. The decrease was dose-dependent from the Candida inoculum and by the concentration of β-D-glucan. A relationship with inhibition of apoptosis was found as the activity of caspase-3 activity, and the level of DNA fragmentation were also decreased. Incubation in the absence/presence of inhibitors showed that the decrease by annexin V expression resulted by activation of the dectin-1 pathway and Raf-1 by β-D glucan. The decrease of annexin V(+)/PI(-) expression was not shown on monocytes of patients with severe sepsis/shock, where no effect of inhibitors was found. Decrease of annexin V binding on monocytes can be viewed as a selective response to C.albicans partly effected through activation of dectin-1. This response is down-regulated after a septic insult.
authors.affiliation: 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Pistiki
authors.affiliation: 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
authors.forename: T
authors.initials: T
authors.lastname: Tsaganos
authors.affiliation: 2nd Department of Critical Care Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
authors.forename: I
authors.initials: I
authors.lastname: Tsangaris
authors.affiliation: 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
authors.forename: N
authors.initials: N
authors.lastname: Antonakos
authors.affiliation: 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
authors.forename: G
authors.initials: G
authors.lastname: Damoraki
authors.affiliation: 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece. egiamarel@med.uoa.gr.|4th Department of Internal Medicine, ATTIKON University Hospital, 1 Rimini Street, 124 62, Athens, Greece. egiamarel@med.uoa.gr.
authors.forename: E J
authors.initials: EJ
authors.lastname: Giamarellos-Bourboulis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017302:Annexins / Q000378:metabolism*; D002176:Candida albicans / Q000276:immunology*; D002448:Cell Adhesion; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology*; D018805:Sepsis / Q000382:microbiology* / Q000473:pathology*; D047071:beta-Glucans / Q000378:metabolism
chemical_list: D017302:Annexins; D047071:beta-Glucans