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Ganguly, K.* ; Upadhyay, S.* ; Irmler, M. ; Takenaka, S. ; Pukelsheim, K.* ; Beckers, J. ; Schulz, H. ; Stöger, T.

Indications of IL1B, IL18 and VEGF cascade in maintenance of homeostasis following transient pulmonary inflammation due to carbon nanoparticle (CNP) challenge in mice .

Vortrag: Herbsttagung der Sektion Zellbiologie, 06-07 November 2009, Borstel, Germany. (2009)
Background: Carbonaceous nanoparticles possess an emerging source of human exposure due to the massive release of combustion products and the ongoing revolution in nanotechnology. The pulmonary inflammation caused by deposited nanoparticles is a key event for their adverse health effects. Epidemiological studies suggest that individuals with favourable lung physiology are at lower risk for particulate matter associated respiratory diseases. Therefore we selected a mouse strain C3H/HeJ (C3) with robust lung physiology and exposed it to moderately toxic carbon nanoparticles (CNP) to study the elicited pulmonary inflammation and its resolution. Methods: 5µg, 20µg and 50µg CNP were intratracheally (i.t.) instilled in C3 mice to identify the optimal dose for subsequent time course studies. Inflammation was assessed using histology, broncheoalveolar lavage (BAL) analysis and by a panel of 62 protein markers to analyze the molecular response. Results: 24h after instillation of CNP, C3 mice exhibited a typical dose response, with the lowest dose (5µg) representing the ‘no effect level’ as reflected by polymorphonuclear leucocyte (PMN) influx, and BAL/lung concentrations of pro-inflammatory cytokines and proteins. Accordingly time course assessment of the inflammatory response was performed after 3 and 7days with 20µg CNP instilled animals. Compared to 24h, BAL PMN counts were significantly decreased at day 3 and by day 7 complete resolution of PMN influx was observed. We have identified protein markers related to   acute response and also for time course response in lung and BAL. After complete resolution of PMN influx on day7, protein concentrations of FGA, CRP, APCS, CCL5, CCL9, FGF2, CCL11, vWF, XCL1, CXCL5, THPO, VEGFA, IL1B, IL18, CSF1, EDN1, CCL3, CCL4, F3 and CD40L were significantly elevated in the lung and BAL. These factors are involved in a closely regulated molecular cascade with IL1b/IL18 at the upstream and FGF2/EDN1/VEGF at the downstream.  BAL-protein concentration and histological analysis did not reveal any evidence of tissue injury in 20µg CNP instilled animals.  Conclusion: Considering the role of VEGF, FGF2 and EDN1 in lung development and morphogenesis together with the lack of any evident tissue damage we suggest a protective/homeostatic machinery is activated to counter the CNP challenge as a precautionary measure.
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Publikationstyp Sonstiges: Vortrag
Korrespondenzautor
Konferenztitel Herbsttagung der Sektion Zellbiologie
Konferzenzdatum 06-07 November 2009
Konferenzort Borstel, Germany
Nichtpatentliteratur Publikationen
Institut(e) Institute of Lung Biology (LHI)