Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on leukocyte function-associated antigen-1 mediated splenocyte adhesion.
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a widespread environmental contaminant that induces various types of immunotoxicity. One effect of exposure to this contaminant is alteration in cell adhesiveness. Leukocyte function-associated antigen-1 (LFA-1) plays an important role not only in T-cell recruitment into sites of inflammation and lymphoid tissues, but also in T-cell activation and in the development of specific immune responses. We, therefore, examined whether the alteration in cell adhesiveness is associated with the modulation of LFA-1 expression and its second messengers following exposure to TCDD. In vitro, 10 nM TCDD exposure suppressed splenocyte adhesion. In addition, the adhesiveness was reduced after in vivo exposure to TCDD (15 microg/kg) for six weeks with a one week interval and after additional in vitro stimulation with anti-CD3. The inhibition of adherence after TCDD exposure was related to a decreased expression of LFA-I, and expression patterns of Rap1 following TCDD exposure correlated with those of LFA-1 expression. However, TCDD did not selectively alter LFA-1 or Rapl expression in T-cell subsets. TCDD caused apparent changes in PI 3-kinase expression levels and the expression patterns of H-Ras correlated with those of PI 3-kinase expression. These data suggest that TCDD exposure down-regulates the conformation and ligand binding affinity of LFA-1 by Rapl and PI 3-kinase signaling pathways with the decreased expression of LFA-1, and consequently leads to a decrease in the LFA-1-mediated adhesion.
Park
Sang-Joon
SJ
Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, Daejeon, 305-600, Korea.
Yoon
Won-Kee
WK
Son
Hwa-Young
HY
Cho
Sung-Whan
SW
Jung
Ju-Young
JY
Jeong
Kyu-Shik
KS
Kim
Tae-Hwan
TH
Kim
Sung-Ho
SH
Ryu
Si-Yun
SY
D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D017931:DNA Primers; D005260:Female; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000187:drug effects*; D020827:rap1 GTP-Binding Proteins / Q000235:genetics
D017931:DNA Primers; D016169:Lymphocyte Function-Associated Antigen-1; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D020827:rap1 GTP-Binding Proteins