This Article Full Text Full Text (PDF) All Versions of this Article: 109/10/1320    most recent 01.CIR.0000118524.62298.E8v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Khandoga, A. Articles by Krombach, F. Search for Related Content PubMed PubMed Citation Articles by Khandoga, A. Articles by Krombach, F. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CARBON CARBON BLACK Related Collections Animal models of human disease Fibrinogen/fibrin Thrombosis risk factors Acute myocardial infarction Platelets Other Research

(Circulation. 2004;109:1320-1325.)
© 2004 American Heart Association, Inc.

Basic Science Reports

Ultrafine Particles Exert Prothrombotic but Not Inflammatory Effects on the Hepatic Microcirculation in Healthy Mice In Vivo

Andrej Khandoga, MD; Andreas Stampfl, MSc; Shinji Takenaka, DVM; Holger Schulz, MD; Roman Radykewicz, BSc; Wolfgang Kreyling, PhD; Fritz Krombach, DVM

From the Institute for Surgical Research, University of Munich, Munich, Germany (A.K., F.K.); and GSF-National Research Center for Environment and Health, Institute of Toxicology (A.S., R.R.), Institute for Inhalation Biology (S.T., H.S., W.K.), and Focus Network Aerosols and Health (W.K.), Neuherberg, Germany.

Correspondence to Prof Dr Fritz Krombach, Institute for Surgical Research, University of Munich, Marchioninistraße 27, D-81377 Munich, Germany. E-mail krombach{at}icf.med.uni-muenchen.de

Received August 14, 2003; revision received November 11, 2003; accepted November 17, 2003.

Background— Air pollution episodes are strongly associated with increased cardiovascular morbidity and mortality. The effect of ultrafine particles (UFPs), when translocated after inhalation, on the microcirculation of extrapulmonary organs remains unclear.

Methods and Results— In C57BL/6 mice, either carbon black UFPs (1x10⁷ and 5x10⁷) or vehicle was infused intra-arterially. Two hours after infusion, platelet- and leukocyte-endothelial cell interactions, sinusoidal perfusion, endothelial fibrin(ogen) deposition, and phagocytic activity of Kupffer cells were analyzed by intravital video fluorescence microscopy in the liver microvasculature. Expression of fibrin(ogen), von Willebrand factor (vWF), and P-selectin on hepatic endothelium was determined by immunostaining. Apoptotic cells were quantified in TUNEL-stained tissue sections. Application of UFPs caused significantly enhanced platelet accumulation on endothelium of postsinusoidal venules and sinusoids in healthy mice. UFP-induced platelet adhesion was not preceded by platelet rolling but was strongly associated with fibrin deposition and an increase in vWF expression on the endothelial surface. In contrast, inflammatory parameters such as the number of rolling/adherent leukocytes, P-selectin expression/translocation, and the number of apoptotic cells were not elevated 2 hours after UFP exposure. In addition, UFPs did not affect sinusoidal perfusion and Kupffer cell function.

Conclusions— UFPs induce platelet accumulation in the hepatic microvasculature of healthy mice that is associated with prothrombotic changes on the endothelial surface of hepatic microvessels. Accumulation of particles in the liver exerts a strong procoagulatory impact but does not trigger an inflammatory reaction and does not induce microvascular/hepatocellular tissue injury.

Key Words: air pollution • platelets • leukocytes • fibrinogen • microcirculation

This article has been cited by other articles:

				A. Nemmar, K. Melghit, and B. H. Ali The Acute Proinflammatory and Prothrombotic Effects of Pulmonary Exposure to Rutile TiO2 Nanorods in Rats Experimental Biology and Medicine, May 1, 2008; 233(5): 610 - 619. [Abstract] [Full Text] [PDF]

				K. Elvevold, B. Smedsrod, and I. Martinez The liver sinusoidal endothelial cell: a cell type of controversial and confusing identity Am J Physiol Gastrointest Liver Physiol, February 1, 2008; 294(2): G391 - G400. [Abstract] [Full Text] [PDF]

				R. Ruckerl, A. Ibald-Mulli, W. Koenig, A. Schneider, G. Woelke, J. Cyrys, J. Heinrich, V. Marder, M. Frampton, H. E. Wichmann, et al. Air Pollution and Markers of Inflammation and Coagulation in Patients with Coronary Heart Disease Am. J. Respir. Crit. Care Med., February 15, 2006; 173(4): 432 - 441. [Abstract] [Full Text] [PDF]

				A. Khandoga, J. S. Kessler, H. Meissner, M. Hanschen, M. Corada, T. Motoike, G. Enders, E. Dejana, and F. Krombach Junctional adhesion molecule-A deficiency increases hepatic ischemia-reperfusion injury despite reduction of neutrophil transendothelial migration Blood, July 15, 2005; 106(2): 725 - 733. [Abstract] [Full Text] [PDF]

				P S Gilmour, E R Morrison, M A Vickers, I Ford, C A Ludlam, M Greaves, K Donaldson, and W MacNee The procoagulant potential of environmental particles (PM10) Occup. Environ. Med., March 1, 2005; 62(3): 164 - 171. [Abstract] [Full Text] [PDF]