Impact of in vitro gallium arsenide exposure on macrophages.
The semiconductor gallium arsenide (GaAs) is classified as an immunotoxicant and a carcinogen. We previously showed that GaAs in vivo induces several phenotypic changes in macrophages located at the exposure site, indicative of an activated state. These physiological alterations may be a primary or secondary consequence of chemical exposure. To discern primary influences, our current study examined the in vitro effects of the chemical on macrophage cell lines and murine peritoneal macrophages. GaAs augmented cathepsins L and B proteolytic activities in all three sources of macrophages. Expression of the two mature isoforms of invariant chain and its cleavage fragment was also significantly increased, indicating that the chemical directly affects macrophages. However, GaAs did not alter the overall cell surface expression of major histocompatibility complex class II molecules on macrophages nor influence their ability to stimulate antigen-specific helper T cell hybridomas to respond to intact antigens that require processing. These findings raise the possibility that the chemical's complete in vivo impact may involve cytokines. Further, GaAs in vitro enhanced steady-state cathepsin L protein, and cathepsins L and B mRNA expression in macrophages, indicating that GaAs may alter gene expression, which may contribute to the chemical's adverse biological effects.
Harrison
M Travis
MT
Department of Microbiology and Immunology, Virginia Commonwealth University, Ricchmond, VA 23298-0678, USA.
Hartmann
Constance B
CB
McCoy
Kathleen L
KL
D000818:Animals; D001152:Arsenicals; D002403:Cathepsins / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D005708:Gallium / Q000633:toxicity*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects
D001152:Arsenicals; D012333:RNA, Messenger; C043055:gallium arsenide; D005708:Gallium; D002403:Cathepsins