Effects of Diesel Exhaust Particles (DEP), Carbon Black, and Silica on Macrophage Responses to Lipopolysaccharide: Evidence of DEP Suppression of Macrophage Activity
Public Domain
-
1999/10/15
-
Details
-
Personal Author:
-
Description:The effects of diesel exhaust particle (DEP) exposure on alveolar macrophage (AM) response to ex vivo and in vivo lipopolysaccharide (LPS) challenge were determined by monitoring LPS-stimulated production of interleukin-1 (IL-1) and tumor necrosis factoralpha (TNF-alpha). The roles of the insoluble particulate and the organic compounds of DEP in altering pulmonary responses were evaluated by comparing the DEP-induced pulmonary responses to those of carbon black (CB), a carbonaceous particle with few adsorbed organic compounds, or to silica, a known pneumotoxic dust. Male Sprague Dawley rats were exposed to a single intratracheal dose (5 or 35 mg/ kg body weight) of DEP, CB, or silica, or to saline vehicle. Rats were sacrificed 1, 3, or 7 d postexposure. To study the responsiveness to the bacterial product LPS, AM isolated from particleexposed rats were challenged ex vivo with LPS (0.1 mug/ 10 6 AM) and LPS-stimulated cytokine release was monitored. In addition, rats were exposed intratracheally to a single dose of DEP (5 mg/kg) and 3 d later exposed in vivo to 1 mg/kg LPS for 3 h prior to measurement of cytokine production by AM. DEP exposure resulted in neutrophil infiltration and elevated levels of albumin and lactate dehydrogenase (LDH) activity in the bronchoalveolar lavage fluid; these responses were not substantially different from those elicited by CB or silica exposure. AM from DEP-exposed rats showed increased spontaneous production of IL-1, but not TNF-alpha, while the opposite was true for CB or silica. Upon ex vivo challenge with LPS, AM from DEP-exposed rats showed a significant decrease in the secretion of TNF- and, to a lesser extent, IL-1, compared to the sum of the DEP and LPS effects. In contrast, AM from CB- or silica-exposed rats did not show this decreased responsiveness to subsequent LPS challenge. This inhibitory action of DEP on LPS-stimulated AM production of IL-1 and TNF- was further confirmed by the results obtained from rats exposed to both DEP and LPS in vivo. In summary, these results indicate that while DEP, CB, and silica all induce pulmonary inflammatory responses due to particle stimulation, only DEP suppress AM cytokine release in response to LPS stimulation. The contrasting cellular response with respect to DEP and CB exposures may be due to the presence of adsorbed organic compounds on DEP, which may contribute to the increased susceptibility of hosts to pulmonary infections after DEP exposure. [Description provided by NIOSH]
-
Subjects:
-
Keywords:
-
ISSN:1528-7394
-
Document Type:
-
Genre:
-
Place as Subject:
-
CIO:
-
Division:
-
Topic:
-
Location:
-
Pages in Document:261-278
-
Volume:58
-
Issue:5
-
NIOSHTIC Number:nn:20027811
-
Citation:J Toxicol Environ Health A 1999 Oct; 58(5):261-278
-
CAS Registry Number:
-
Federal Fiscal Year:2000
-
Peer Reviewed:True
-
Source Full Name:Journal of Toxicology and Environmental Health, Part A: Current Issues
-
Collection(s):
-
Main Document Checksum:urn:sha-512:2c6ef6a99acdcc030401872f62203f7234ee1959c540a782ccfb1ab3f6c9e1fbaae79e1290c76eaba4f7edfc3c422089ae64978e7887b044ecca6eee400d5efa
-
Download URL:
-
File Type:
ON THIS PAGE
CDC STACKS serves as an archival repository of CDC-published products including
scientific findings,
journal articles, guidelines, recommendations, or other public health information authored or
co-authored by CDC or funded partners.
As a repository, CDC STACKS retains documents in their original published format to ensure public access to scientific information.
As a repository, CDC STACKS retains documents in their original published format to ensure public access to scientific information.
You May Also Like