MEETING ABSTRACT Open Access Endotoxin-induced microparticle formation is subject to tolerance development in humans Daniel Nguyen, Stefan Weisshaar, Michael Wolzt * From 16th Scientific Symposium of the Austrian Pharmacological Society (APHAR) Vienna, Austria. 25-27 November 2010 Background Microparticles (MP) are small membrane vesicles expressing tissue factor and staining positive for annexin V which are released from different cell types during cell activation and apoptosis. MP are considered to pro- mote coagulation and impair vascular function. Circulat- ing concentrations of MP are elevated in patients with systemic inflammatory conditions. Methods Formation of MP was studied in 8 healthy male subjects exposed to intravenous E. coli endotoxin (LPS; 2 ng/kg body weight) who were re-challenged after 17 ± 11 days. In addition, intravenous vitamin C (25 g) or placebo was administered 3.5 hours after LPS on alternate trial days in random order. Venous blood samples were taken before, 3 h and 6 h after LPS administration. MP were detected using FACS analysis. Leukocyte count and body temperature were measured as positive control. All results are expressed in medians in the unit 10 3 MP/μL plasma. Results MP formation was increased 3 h and 6 h after LPS administration. However, this effect was only demon- strable after the first LPS challenge with an increase of MP from baseline 596 units [range 399–1704 units] by a factor of 1.05 at 3 h and 3.87 at 6 h after LPS, and abol- ished after the second LPS exposure with a decrease from 874 units [430–1404 units] by a factor of 1.17 at 3 h and 1.25 at 6 h. This increase was independent of vitamin C administration. In contrast, reactivity of body temperature and leukocytosis 3 h and 6 h after LPS was similar between the study periods. Conclusions Our results demonstrate rapid and marked formation of MP in healthy men after systemic LPS challenge. The development of tolerance to LPS is observed in the absence of mitigated systemic inflammatory responses. This suggests that MP formation follows different path- ways than those of inflammatory mechanisms. Published: 16 November 2010 doi:10.1186/1471-2210-10-S1-A37 Cite this article as: Nguyen et al.: Endotoxin-induced microparticle formation is subject to tolerance development in humans. BMC Pharmacology 2010 10(Suppl 1):A37. Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color ﬁgure charges • Immediate publication on acceptance • Inclusion in PubMed, CAS, Scopus and Google Scholar • Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit * Correspondence: [email protected] Department of Clinical Pharmacology, Medical University of Vienna, 1090 Vienna, Austria Nguyen et al. BMC Pharmacology 2010, 10(Suppl 1):A37 http://www.biomedcentral.com/1471-2210/10/S1/A37 © 2010 Wolzt et al; licensee BioMed Central Ltd.

Endotoxin-induced microparticle formation is subject to tolerance development in humans

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Page 1: Endotoxin-induced microparticle formation is subject to tolerance development in humans

MEETING ABSTRACT Open Access

Endotoxin-induced microparticle formation issubject to tolerance development in humansDaniel Nguyen, Stefan Weisshaar, Michael Wolzt*

From 16th Scientific Symposium of the Austrian Pharmacological Society (APHAR)Vienna, Austria. 25-27 November 2010

BackgroundMicroparticles (MP) are small membrane vesiclesexpressing tissue factor and staining positive for annexinV which are released from different cell types duringcell activation and apoptosis. MP are considered to pro-mote coagulation and impair vascular function. Circulat-ing concentrations of MP are elevated in patients withsystemic inflammatory conditions.

MethodsFormation of MP was studied in 8 healthy male subjectsexposed to intravenous E. coli endotoxin (LPS; 2 ng/kgbody weight) who were re-challenged after 17 ± 11 days.In addition, intravenous vitamin C (25 g) or placebo wasadministered 3.5 hours after LPS on alternate trial daysin random order. Venous blood samples were takenbefore, 3 h and 6 h after LPS administration. MP weredetected using FACS analysis. Leukocyte count andbody temperature were measured as positive control. Allresults are expressed in medians in the unit 103 MP/μLplasma.

ResultsMP formation was increased 3 h and 6 h after LPSadministration. However, this effect was only demon-strable after the first LPS challenge with an increase ofMP from baseline 596 units [range 399–1704 units] by afactor of 1.05 at 3 h and 3.87 at 6 h after LPS, and abol-ished after the second LPS exposure with a decreasefrom 874 units [430–1404 units] by a factor of 1.17 at3 h and 1.25 at 6 h. This increase was independent ofvitamin C administration. In contrast, reactivity of body

temperature and leukocytosis 3 h and 6 h after LPS wassimilar between the study periods.

ConclusionsOur results demonstrate rapid and marked formation ofMP in healthy men after systemic LPS challenge. Thedevelopment of tolerance to LPS is observed in theabsence of mitigated systemic inflammatory responses.This suggests that MP formation follows different path-ways than those of inflammatory mechanisms.

Published: 16 November 2010

doi:10.1186/1471-2210-10-S1-A37Cite this article as: Nguyen et al.: Endotoxin-induced microparticleformation is subject to tolerance development in humans. BMCPharmacology 2010 10(Suppl 1):A37.

Submit your next manuscript to BioMed Centraland take full advantage of:

• Convenient online submission

• Thorough peer review

• No space constraints or color figure charges

• Immediate publication on acceptance

• Inclusion in PubMed, CAS, Scopus and Google Scholar

• Research which is freely available for redistribution

Submit your manuscript at www.biomedcentral.com/submit

* Correspondence: [email protected] of Clinical Pharmacology, Medical University of Vienna, 1090Vienna, Austria

Nguyen et al. BMC Pharmacology 2010, 10(Suppl 1):A37http://www.biomedcentral.com/1471-2210/10/S1/A37

mailto:[email protected]