Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-10-3
pubmed:abstractText
Dichloroacetyl chloride (DCAC) is formed from trichloroethene (TCE), which is implicated in inducing/accelerating autoimmune response. Due to its potent acylating activity, DCAC may convert proteins to neo-antigens and thus could induce autoimmune responses. Dichloroacetic anhydride (DCAA), which is a similar acylating agent, might also induce autoimmune responses. To evaluate if chloroacylation plays a role in the induction of autoimmunity, we have measured the autoimmune responses following treatment with DCAC or DCAA in autoimmune-prone MRL+/+ mice. Five-week-old female mice were injected intraperitoneally (twice weekly) with 0.2 mmol/kg of DCAC or DCAA in corn oil for 6 weeks. Total serum IgG, IgG1, and IgE levels were significantly increased in DCAC-treated mice as compared to controls. These increases corresponded with increases in DCAC-specific IgG and IgG1 levels. Total serum IgM was decreased in both DCAC- and DCAA-treated mice. Antinuclear antibodies, measured as an indication of systemic autoimmune responses, were increased in both DCAC- and DCAA-treated mice. Of eight Th1/Th2 cytokines measured in the serum, only IL-5 was significantly decreased in both treatment groups. The cytokine secretion patterns of splenic lymphocytes after stimulation with antibodies against CD3 (T cell receptor-mediated signal) and CD28 (costimulatory signal) differed between treatment and control groups. Levels of IL-1, IL-3, IL-6, IFN-gamma, G-CSF, and KC were higher in cultures of stimulated splenocytes from either DCAC- or DCAA-treated mice than from controls. The level of IL-17 was only increased in cultures from DCAC-treated mice. Increased lymphocytic populations were found in the red pulp of spleens following treatment with either DCAC or DCAA. In addition, thickening of the alveolar septa in the lungs of DCAC- or DCAA-treated mice was observed. The lung histopathology in exposed mice was consistent with the symptomology observed in welders exposed to DCAC/phosgene. Thickening was more pronounced in DCAC-treated mice. Our data suggest that DCAC and DCAA elicit autoimmune responses in MRL+/+ mice that might be reflective of their chloroacylation potential in vivo.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0041-008X
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
216
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
248-55
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16806339-Acetic Acids, pubmed-meshheading:16806339-Acetic Anhydrides, pubmed-meshheading:16806339-Animals, pubmed-meshheading:16806339-Antibodies, Antinuclear, pubmed-meshheading:16806339-Antibodies, Blocking, pubmed-meshheading:16806339-Antigens, CD28, pubmed-meshheading:16806339-Antigens, CD3, pubmed-meshheading:16806339-Autoimmunity, pubmed-meshheading:16806339-Cells, Cultured, pubmed-meshheading:16806339-Cytokines, pubmed-meshheading:16806339-Dichloroacetate, pubmed-meshheading:16806339-Female, pubmed-meshheading:16806339-Homozygote, pubmed-meshheading:16806339-Immunoglobulins, pubmed-meshheading:16806339-Lymphocytes, pubmed-meshheading:16806339-Mice, pubmed-meshheading:16806339-Mice, Inbred MRL lpr, pubmed-meshheading:16806339-Pulmonary Alveoli, pubmed-meshheading:16806339-Spleen
pubmed:year
2006
pubmed:articleTitle
Autoimmune response in MRL+/+ mice following treatment with dichloroacetyl chloride or dichloroacetic anhydride.
pubmed:affiliation
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555-0609, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural