Platelet adhesion and fibrinogen deposition in murine microvessels upon inhalation of nanosized carbon particles.
BACKGROUND
The translocation of nanoparticles in the lung toward effector organs via the circulation is considered an important direct pathway for systemic effects of nanoparticles after inhalation. Recently, we have reported that a moderate dose of systemically administered nanosized carbon black particles exerted thrombogenic effects in hepatic microvessels of healthy mice.


OBJECTIVE
This study addresses the questions of whether similar thrombogenic effects are also evoked upon inhalation of nanosized carbon particles (NCP) and whether NCP-induced hepatic platelet accumulation is associated with pulmonary or systemic inflammation.


METHODS
Two and 8 h after a 24-h exposure to either filtered air or to NCP, intravital fluorescence microscopy of the hepatic microcirculation was performed in C57Bl/6 mice. Parameters of pulmonary or systemic inflammatory response were determined in bronchoalveolar lavage and blood/plasma samples.


RESULTS
Inhalative exposure to NCP caused platelet accumulation in the hepatic microvasculature, whereas leukocyte recruitment and sinusoidal perfusion did not differ from controls. Fibrinogen deposition was detected by immunohistochemistry in both hepatic and cardiac microvessels from NCP-exposed mice. In contrast, inhalation of NCP affected neither the plasma levels of proinflammatory cytokines nor blood cell counts. Moreover, the bronchoalveolar lavage data indicate that no significant inflammatory response occurred in the lung.


CONCLUSIONS
Thus, exposure to NCP exerts thrombogenic effects in the microcirculation of healthy mice independent of the route of administration (i.e. inhalation or systemic intra-arterial administration). The NCP-induced thrombogenic effects are not liver specific, are associated with neither a local nor a systemic inflammatory response, and seem to be independent of pulmonary inflammation.
Khandoga
A
A
Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universität München, München, Germany. Andrej.Khandoga@med.uni-muenchen.de
Stoeger
T
T
Khandoga
A G
AG
Bihari
P
P
Karg
E
E
Ettehadieh
D
D
Lakatos
S
S
Fent
J
J
Schulz
H
H
Krombach
F
F
D000280:Administration, Inhalation; D000818:Animals; D001692:Biological Transport; D002244:Carbon / Q000009:adverse effects*; D005340:Fibrinogen / Q000378:metabolism*; D007249:Inflammation; D008099:Liver / Q000098:blood supply; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation; D053758:Nanoparticles / Q000009:adverse effects*; D010973:Platelet Adhesiveness; D013927:Thrombosis; D014018:Tissue Distribution
D002244:Carbon; D005340:Fibrinogen