Ochratoxin A inhibits the production of tissue factor and plasminogen activator inhibitor-2 by human blood mononuclear cells: another potential mechanism of immune-suppression.
The mycotoxin ochratoxin A (OTA), an ubiquitous contaminant of food products endowed with a wide spectrum of toxicity, affects several functions of mononuclear leukocytes. Monocytes/macrophages play a major role in fibrin accumulation associated with immune-inflammatory processes through the production of tissue factor (TF) and plasminogen activator inhibitor 2 (PAI-2). We studied the effect of OTA on TF and PAI-2 production by human blood mononuclear cells (MNC). The cells were incubated for 3 or 18 h at 37 degrees C with non toxic OTA concentrations in the absence and in the presence of lipopolysaccharide (LPS) or other inflammatory agents. TF activity was measured by a one-stage clotting test. Antigen assays were performed by specific ELISAs in cell extracts or conditioned media and specific mRNAs were assessed by RT-PCR. OTA had no direct effect on TF and PAI-2 production by MNC. However, OTA caused a dose-dependent reduction in LPS-induced TF (activity, antigen and mRNA) and PAI-2 (antigen and mRNA) production with >85% inhibition at 1 mug/ml. Similar results were obtained when monocyte-enriched preparations were used instead of MNC. TF production was also impaired by OTA (1 mug/ml) when MNC were stimulated with phorbol myristate acetate (98% inhibition), IL-1beta (83%) or TNF-alpha (62%). The inhibition of TF and PAI-2 induction might represent a hitherto unrecognized mechanism whereby OTA exerts immunosuppressant activity.
Rossiello
Maria R
MR
Department of Biomedical Sciences and Human Oncology, Section of General and Experimental Pathology, University of Bari, Policlinico, Piazza G. Cesare 11, 70124 Bari, Italy.
Rotunno
Crescenzia
C
Coluccia
Addolorata
A
Carratù
Maria R
MR
Di Santo
Angelomaria
A
Evangelista
Virgilio
V
Semeraro
Nicola
N
Colucci
Mario
M
D001483:Base Sequence; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D009183:Mycotoxins / Q000633:toxicity*; D009793:Ochratoxins / Q000633:toxicity; D017396:Plasminogen Activator Inhibitor 2 / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013925:Thromboplastin / Q000096:biosynthesis*
D017931:DNA Primers; D009183:Mycotoxins; D009793:Ochratoxins; D017396:Plasminogen Activator Inhibitor 2; C025589:ochratoxin A; D013925:Thromboplastin