title: Particle-induced pulmonary acute phase response may be the causal link between particle inhalation and cardiovascular disease.
abstract: Inhalation of ambient and workplace particulate air pollution is associated with increased risk of cardiovascular disease. One proposed mechanism for this association is that pulmonary inflammation induces a hepatic acute phase response, which increases risk of cardiovascular disease. Induction of the acute phase response is intimately linked to risk of cardiovascular disease as shown in both epidemiological and animal studies. Indeed, blood levels of acute phase proteins, such as C-reactive protein and serum amyloid A, are independent predictors of risk of cardiovascular disease in prospective epidemiological studies. In this review, we present and review emerging evidence that inhalation of particles (e.g., air diesel exhaust particles and nanoparticles) induces a pulmonary acute phase response, and propose that this induction constitutes the causal link between particle inhalation and risk of cardiovascular disease. Increased levels of acute phase mRNA and proteins in lung tissues, bronchoalveolar lavage fluid and plasma clearly indicate pulmonary acute phase response following pulmonary deposition of different kinds of particles including diesel exhaust particles, nanoparticles, and carbon nanotubes. The pulmonary acute phase response is dose-dependent and long lasting. Conversely, the hepatic acute phase response is reduced relative to lung or entirely absent. We also provide evidence that pulmonary inflammation, as measured by neutrophil influx, is a predictor of the acute phase response and that the total surface area of deposited particles correlates with the pulmonary acute phase response. We discuss the implications of these findings in relation to occupational exposure to nanoparticles.
authors.affiliation: National Research Centre for the Working Environment, Copenhagen, Denmark.
authors.forename: Anne T
authors.initials: AT
authors.lastname: Saber
authors.forename: Nicklas R
authors.initials: NR
authors.lastname: Jacobsen
authors.forename: Petra
authors.initials: P
authors.lastname: Jackson
authors.forename: Sarah Søs
authors.initials: SS
authors.lastname: Poulsen
authors.forename: Zdenka O
authors.initials: ZO
authors.lastname: Kyjovska
authors.forename: Sabina
authors.initials: S
authors.lastname: Halappanavar
authors.forename: Carole L
authors.initials: CL
authors.lastname: Yauk
authors.forename: Håkan
authors.initials: H
authors.lastname: Wallin
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
mesh_terms: D000210:Acute-Phase Reaction; D000818:Animals; D002318:Cardiovascular Diseases; D006801:Humans; D019570:Inhalation Exposure; D051379:Mice; D053758:Nanoparticles; D016273:Occupational Exposure