Alveolar macrophage responses to fine and ultrafine particles

Faculty Researcher: Peter Mancuso, PhD, Assistant Professor of Environmental Health Sciences at the University of Michigan

This project is an important first step in understanding the characteristics of exposure, dose, and the adverse health effects associated with inhalable particulates finer than those contained within the particle size fractions embodied in current occupational aerosol standards. The objective of the research is to examine the interaction of alveolar macrophages with fine and ultrafine particles in order to identify the factors such as particle size and chemical composition that govern particulate uptake and subsequent inflammatory mediator synthesis. Specifically the project will (a) examine the interactions between insoluble particles (polystyrene microspheres) and murine alveolar macrophages in vitro, using the confocal microscopy to examine the uptake of particles of different sizes and chemical composition; and (b) correlate particulate uptake with the synthesis of pro-inflammatory cytokines and leukotrienes that are relevant to health effects (such as exacerbations of asthma) known to be associated with exposures of humans to fine aerosols. The outcome of this research will be new experimental data that will begin to help elucidate the nature of how inhaled fine particles can produce inflammatory responses that might lead to the observed adverse health effects in exposed populations. Since no previous research has addressed in vitro the nature of the interactions in question at this level, the important distinctive roles of particle size and chemical composition remain unclear. An important outcome of the research will be the basis it will provide for a viable proposal for much larger external funding (e.g., one or more RO1s), to support far more extensive research both in vitro and in vivo.

Grants resulting from this project:
University of Michigan Tobacco Research Network. The effect of low tar cigarette exposure on pulmonary antibacterial host defense. 9/1/04-8/30/05.

Research trainee’s current position:
Peter Mancuso is currently an Associate Professor of Environmental Health Sciences at the University of Michigan.