Gallium arsenide modulates proteolytic cathepsin activities and antigen processing by macrophages.
Gallium arsenide (GaAs) is a semiconductor utilized in the electronics industry. Chemical exposure of animals causes a local inflammatory reaction, but systemic immunosuppression. Mice were administered i.p. 200 mg/kg GaAs crystals or latex beads, or vehicle. Five days after exposure, splenic macrophages were defective, whereas thioglycolate-elicited peritoneal macrophages (PEC) were more efficient in processing the Ag, pigeon cytochrome c, than vehicle control macrophages. Various aspects of the MHC class II Ag-processing pathway were examined. Both macrophage populations normally presented a peptide fragment to the CD4+ T cells. Surface MHC class II expression on the PEC was up-regulated, but splenic cells had normal MHC class II expression. PEC had elevated levels of glutathione and cysteine, major physiologic reducing thiols. However, the cysteine content of splenic macrophages was diminished. Proteolytic activities of aspartyl cathepsin D, and thiol cathepsins B and L were decreased significantly in splenic macrophages. On the other hand, thiol cathepsin activities were increased selectively in PEC. Latex bead-exposed PEC were not more potent APC, and their thiol cathepsin activities were unchanged, indicating that phagocytosis and nonspecific irritation were not responsible. The phenotype of PEC directly exposed to GaAs mirrored cytokine-activated macrophages, in contrast to splenic macrophages from a distant site. Therefore, GaAs exposure differentially modulated cathepsin activities in splenic macrophages and PEC, which correlated with their Ag-processing efficiency. Perhaps such distinct alterations may contribute to the local inflammation and systemic immunotoxicity caused by chemical exposure.
Lewis
T A
TA
Department of Microbiology and Immunology, Virginia Commonwealth University/Medical College of Virginia, Richmond 23298, USA.
Hartmann
C B
CB
McCoy
K L
KL
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D001152:Arsenicals / Q000008:administration & dosage / Q000494:pharmacology*; D002403:Cathepsins / Q000187:drug effects / Q000378:metabolism*; D003433:Crosses, Genetic; D010450:Endopeptidases / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D005260:Female; D005708:Gallium / Q000008:administration & dosage / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D013438:Sulfhydryl Compounds / Q000378:metabolism
D000276:Adjuvants, Immunologic; D001152:Arsenicals; D000949:Histocompatibility Antigens Class II; D013438:Sulfhydryl Compounds; C043055:gallium arsenide; D005708:Gallium; D002403:Cathepsins; D010450:Endopeptidases