**Acknowledgements**

**14. Environmental exposure to particle inhalation**

sary [151].

42 Lung Inflammation

**15. Conclusion**

Epidemiologic and occupational studies show that exposure to high concentrations of ambient particulate matter cause cardiopulmonary health effects, including exacerbation of preexisting lung disease as well as the development of respiratory infections. Particle related oxidative stress and inflammatory responses are considered to be key for the subsequent health effects, but the precise mechanism how inhaled poorly soluble, sterile, endotoxin free particle induce pulmonary inflammation is not well understood [150]. Since the size of the inhaled material determines their penetration depth into the lungs, smaller particle (<100nm) cause higher alveolar lung burden than bigger sized particles. Lung surface macrophages (i.e. AMs) do not efficiently phagocytose small, sub-100nm sized, so called ultrafine particles (UFP) or nanoparticles (NP), but take them up in a rather sporadic and unspecific way [151]. But the evidence that UFP bypass the most important clearance mechanism for particles deposited in the alveoli, namely phagocytic uptake by macrophages, requires further clarification as to whether these results are specific for the material, the size or other characteristics of the particles. A rethinking of clearance pathways for inhaled UFP is therefore considered neces‐

Inhalation of ultrafine carbon particles triggers a biphasic pro-inflammatory process in the lung, involving the activation of macrophages and the upregulation of immunomodulatory proteins [152]. Higher doses cause a distinct inflammatory response characterized by the release of pro-inflammatory cytokines and accumulation of inflammatory leukocytes [153]. A single exposure to these carbon particles however causes only a transient inflammatory response, which resolves within one week after treatment [154]. Black carbon laden AMs however are observed even at much later time points when no inflammatory stimulation in the lungs is detectable. Whether the immunological activity of these long-living tissue macrophages gets changed remains unknown. In animal experiments, when lung inflamma‐ tion for example is induced by titanium di oxide (TiO2) particles in rats, AMs induce the production of IL-13 and IL-25 production. This in turn modulates the inflammatory response [155]. When exposed to gold NPs, it is found that AMs efficiently internalize NPs by endocy‐ tosis, and rearrangements of vesicles and of NPs within the vesicles of macrophages occurred [156]. The uptake of gold particles by AMs is limited, though to a low degree, systemic particle translocation is reported. To summarise, inhaled NPs or UFPs pose high burden to the integrity of lungs as these particles penetrate into the susceptible alveolar region due to the ineffective clearance mechanisms. Whether an activation of lung macrophages, potentially caused by particle-cell interactions, results in a change of their immunological properties thereby

increasing the susceptibility for secondary infection warrants further investigations.

Macrophages are essential to host defense mechanism. The alveolar macrophages exhibit unique properties, including uncharacteristic phenotypic features, remarkable plasticity and (S.U.) CSIR-SRA (13-8553A)-2012/POOL
