We also observed semiquantitative differences between the type of PM exposure and the relative frequency of macrophages that were seen to have obvious particle residues present in their cytoplasm (fig.3b). DEP activated DC in vivo and provoked a Th2 response ex vivo. By contrast, CBP and AgP induced altered lung tissue barrier integrity but failed to stimulate CD4+ T cells as effectively. Our work suggests that respirable pollutants activate the innate immune response with enhanced DC activation, pulmonary inflammation and Th2-immune responsiveness. Key Words:Innate immunity, Allergic immunity, Dendritic cell, Lung, Inflammation, Immunotoxicology, Toxicology, Particulate matter, Nanoparticles == Introduction Rabbit Polyclonal to B4GALNT1 == The immune pathology of asthma is defined in part by airway hyperresponsiveness and a deregulated pattern of Th2 cytokine release including interleukin (IL)-4, IL-5 and IL-13 [1,2,3,4]. Several studies also support a Th1 component (e.g. secretion of interferon-, IFN-) in asthma [5,6]. Environmental cues such as ambient particulate matter (APM) and diesel exhaust particles (DEP, an emission source PM) stimulate adaptive and innate immunity in asthma [3,5,6,7,8,9]. The modulation of lung innate immunity by biologically, chemically or structurally disparate particulate matter (PM) species that can breach the airway barrier and interact with host immunity is important. Environmental PM is a complex mixture of particles with varying properties. How the properties of exposure to PM contribute to altered early pulmonary immune responses and dendritic cell (DC) activation in vivo are unclear but may be attributable to cellular contact-dependent particle size and surface area of the PM species, elemental and hydrocarbon constitution and an inherent ability to differentially promote oxidative stress and acute inflammation [10,11,12,13,14]. The airway wall is a biologically complex cellular barrier that is considered a major arm of the innate immune system, and maintains the lung as an immune-privileged organ [15]. Interdigitated throughout the respiratory epithelium are specialized macrophages and professional antigen-presenting DC subsets [15,16,17]. Airway inflammation in allergic asthma reflects an aberrant immune response against otherwise harmless inhaled allergens. Although DCs are regularly distributed throughout the bronchial epithelium and parenchyma, little is known about how inhaled environmental exposures affect the activation of DCs. We have shown that APM, environmental DEP or a common allergen (e.g. ragweed extract) instructs non-classic DC maturation enabling them to stimulate a complex pattern of Th1- and Th2-associated responses [6,12,18,19]. The exact location of where DCs sample respirable antigen in the lung remains ill-defined [15,16], although it is known that DC serve a key role in the immune pathology of allergic asthma [20,21,22]. The lung is known to benefit from the functions of two major subsets of DC, termed conventional myeloid DC (mDC), that express moderate to high Pipequaline hydrochloride levels of both CD11c+ and CD11b+, and a second subpopulation, termed plasmacytoid DC (pDC), that display cell-surface expression of PDCA-1 and low levels of CD11c [23,24,25,26,27]. Studiesexploring the role of DC activation and allergic risk in asthma development have focused on the adjuvant potential of PM to induce allergic sensitization to a coadministered antigen-like ovalbumin (OVA) or house dust mite [6,12,18,28,29,30,31,32]. Often high and repeated doses of PM exposure are used that also induce tissue Pipequaline hydrochloride damage and general airway inflammation. In this report we hypothesized that single acute exposure to ambient or engineered PM in the absence of an additional immune adjuvant Pipequaline hydrochloride would promote activation of lung DC in vivo, particularly at the levels of differential markers of pulmonary inflammation, particle uptake in the lung and activation of DC in vivo. We have previously conducted detailed in vitro studies of the effects of PM on human and.