Alteration of pulmonary immunity to Listeria monocytogenes by diesel exhaust particles (DEPs). I. Effects of DEPs on early pulmonary responses.
It has been hypothesized that diesel exhaust particles (DEPs) aggravate pulmonary bacterial infection by both innate and cell-mediated immune mechanisms. To test this hypothesis, we investigated the effects of DEP exposure on the functions of alveolar macrophages (AMs) and lymphocytes from lung-draining lymph nodes using a rat Listeria monocytogenes infection model. In the present study, we focused on the effects of DEP exposure on AM functions, including phagocytic activity and secretion of proinflammatory cytokines. The Listeria infection model was characterized by an increase in neutrophil count, albumin content, and acellular lactate dehydrogenase activity in the bronchoalveolar lavage (BAL) fluid at 3 and 7 days postinfection. Short-term DEP inhalation (50 and 100 mg/m(3), 4 hr) resulted in a dose-dependent suppression of lung clearance of Listeria, with the highest bacteria count occurring at day 3. This aggravated bacterial infection was consistent with the inhibitory effect of DEPs on macrophage functions. DEPs suppressed phagocytosis and Listeria-induced basal secretion of interleukin-1ss (IL-1ss) and IL-12 by AMs in a dose-dependent manner. The amount of IL-1ss and IL-12 in the BAL fluid was also reduced by DEP exposure. In addition, DEPs decreased Listeria-induced lipopolysaccharide-stimulated secretion of tumor necrosis factor-alpha (TNF-alpha), IL-1ss, and IL-12 from AMs. These results suggest that DEPs retard bacterial clearance by inhibiting AM phagocytosis and weaken the innate immunity by inhibiting AM secretion of IL-1ss and TNF-alpha. DEPs may also suppress cell-mediated immunity by inhibiting AM secretion of IL-12, a key cytokine for the initiation of T helper type 1 cell development in Listeria infection.
Yin
Xue-Jun
XJ
School of Pharmacy, West Virginia University, Morgantown, West Virginia 26506-9530, USA.
Schafer
Rosana
R
Ma
Jane Y C
JY
Antonini
James M
JM
Weissman
David D
DD
Siegel
Paul D
PD
Barger
Mark W
MW
Roberts
Jenny R
JR
Ma
Joseph K-H
JK
D000818:Animals; D016207:Cytokines / Q000276:immunology / Q000494:pharmacology; D004195:Disease Models, Animal; D006801:Humans; D019570:Inhalation Exposure; D008089:Listeria monocytogenes / Q000472:pathogenicity*; D008088:Listeriosis / Q000276:immunology* / Q000503:physiopathology; D008214:Lymphocytes / Q000502:physiology; D016676:Macrophages, Alveolar / Q000502:physiology*; D008297:Male; D016273:Occupational Exposure; D010587:Phagocytosis; D051381:Rats; D001335:Vehicle Emissions / Q000009:adverse effects*
D016207:Cytokines; D001335:Vehicle Emissions