title: Diesel exhaust particles induce aberrant alveolar epithelial directed cell movement by disruption of polarity mechanisms.
abstract: Disruption of the respiratory epithelium contributes to the progression of a variety of respiratory diseases that are aggravated by exposure to air pollutants, specifically traffic-based pollutants such as diesel exhaust particles (DEP). Recognizing that lung repair following injury requires efficient and directed alveolar epithelial cell migration, this study's goal was to understand the mechanisms underlying alveolar epithelial cells response to DEP, particularly when exposure is accompanied with comorbid lung injury. Separate mechanistic steps of directed migration were investigated in confluent murine LA-4 cells exposed to noncytotoxic concentrations (0-100 μg/cm(2)) of either automobile-emitted diesel exhaust particles (DEP(A)) or carbon black (CB) particles. A scratch wound model ascertained how DEP(A) exposure affected directional cell migration and BCECF ratio fluorimetry-monitored intracellular pH (pHi). Cells were immunostained with giantin to assess cell polarity, and with paxillin to assess focal cell adhesions. Cells were immunoblotted for ezrin/radixin/moesin (ERM) to assess cytoskeletal anchoring. Data demonstrate herein that exposure of LA-4 cells to DEP(A) (but not CB) resulted in delayed directional cell migration, impaired de-adhesion of the trailing edge cell processes, disrupted regulation of pHi, and altered Golgi polarity of leading edge cells, along with modified focal adhesions and reduced ERM levels, indicative of decreased cytoskeletal anchoring. The ability of DEP(A) to disrupt directed cell migration at multiple levels suggests that signaling pathways such as ERM/Rho are critical for transduction of ion transport signals into cytoskeletal arrangement responses. These results provide insights into the mechanisms by which chronic exposure to traffic-based emissions may result in decrements in lung capacity.
authors.affiliation: Department of Biological Sciences, College of Arts and Sciences, Florida Gulf Coast University, Fort Myers, Florida 33965, USA. alagier@fgcu.edu
authors.forename: Adriana J
authors.initials: AJ
authors.lastname: LaGier
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Manzo
authors.forename: Janice A
authors.initials: JA
authors.lastname: Dye
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D056809:Alveolar Epithelial Cells / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D016764:Cell Polarity / Q000187:drug effects*; D002478:Cells, Cultured; D005470:Fluorometry; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D015151:Immunoblotting; D051379:Mice; D052638:Particulate Matter / Q000633:toxicity*; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D053260:Soot / Q000633:toxicity; D001335:Vehicle Emissions / Q000633:toxicity*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000393:Air Pollutants; D015415:Biomarkers; D052638:Particulate Matter; D053260:Soot; D001335:Vehicle Emissions