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(Journal of Leukocyte Biology. 2001;69:639-644.)
© 2001 by Society for Leukocyte Biology

Inflammatory macrophage nuclear factor-B and proteasome activity are inhibited following exposure to inhaled isobutyl nitrite

Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas

Correspondence: Lee S. F. Soderberg, Ph.D., Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205. E-mail: Soderberglees{at}exchange.uams.edu

A history of abuse of nitrite inhalants has been correlated with HIV seropositivity and Kaposi’s sarcoma. A series of 14 daily, 45-min exposures of mice to 900-ppm isobutyl nitrite in an inhalation chamber reduced the number of peritoneal exudate macrophages (PEM) by 35% and the number of resident peritoneal macrophages (RPM) by 18%. Although the tumoricidal activity of RPM was not affected by the inhalant, the cytotoxicity of PEM was reduced by 26%. The induction of nitric oxide (NO) and the inducible NO synthase (iNOS) protein in PEM were inhibited by the inhalant to a similar extent. Inhibition of NF-B activation in PEM from mice exposed to the inhalant corresponded to reduced degradation of the NF-B inhibitor, IB. Proteasome-associated, enzymatic activity was compromised in PEM from inhalant-exposed mice, suggesting that inhaled isobutyl nitrite compromised macrophage, tumoricidal activity by inhibiting proteasomal degradation of the NF-B inhibitor, IB.

Key Words: inhalant • signal transduction • immunosuppression • Kaposi’s sarcoma • AIDS

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