Delta(9)-tetrahydrocannabinol selectively increases aspartyl cathepsin D proteolytic activity and impairs lysozyme processing by macrophages.
Delta(9)-tetrahydrocannabinol (THC) causes an antigen-dependent defect in the ability of macrophages to activate helper T cells, and this drug-induced impairment is mediated through the peripheral CB2 receptor. Various requirements for the processing of the antigen, lysozyme, were examined to determine where along the pathway THC exerts its influence. A THC-exposed macrophage hybridoma inefficiently stimulated interleukin-2 secretion by a helper T cell hybridoma in response to native lysozyme and its reduced form, suggesting that disulfide bond reduction was unaffected. Cell surface expression of major histocompatibility complex class II molecules was normal on THC-exposed macrophages. The drug-exposed macrophages also competently presented a lysozyme peptide to the T cells, indicating that the class II molecules were functional. The proteolytic activity of two thiol cathepsins was unaltered, but aspartyl cathepsin D activity was significantly increased in THC-exposed macrophages. Thus, selective up-regulation of aspartyl cathepsin activity accompanied the deficiency in lysozyme processing and may contribute, at least in part, to the antigen-dependent processing defect in THC-exposed macrophages.
Matveyeva
M
M
Department of Microbiology and Immunology, Virginia Commonwealth University, Box 980678, Richmond, VA 23298-0678, USA.
Hartmann
C B
CB
Harrison
M T
MT
Cabral
G A
GA
McCoy
K L
KL
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D002402:Cathepsin D / Q000378:metabolism*; D002478:Cells, Cultured; D013759:Dronabinol / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009113:Muramidase / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects
D000949:Histocompatibility Antigens Class II; D013759:Dronabinol; D009113:Muramidase; D002402:Cathepsin D