Am. J. Respir. Cell Mol. Biol., Volume 22, Number 2, February, 2000 200-208

Adhesion and Pollution Particle-Induced Oxidant Generation Is neither Necessary nor Sufficient for Cytokine Induction in Human Alveolar Macrophages

Krishna Mondal, J. Stephen Haskill, and Susanne Becker

Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill; and United States Environmental Protection Agency National Health and Environmental Effects Research Laboratory, Research Triangle Park, North Carolina

Adhesion of human monocytes (MOs) results in the rapid transcriptional activation of cytokine genes that are dependent on nuclear factor (NF)-B. Several pathways leading to activation of NF-B have been described, including those involving reactive oxygen intermediates (ROIs) and members of the mitogen-activated protein (MAP) kinase superfamily. To investigate the involvement of tyrosine phosphorylation (TP) and oxidant generation in interleukin (IL)-8 and GRO messenger RNA induction, MOs and human alveolar macrophages (AMs) were adhered to plastic or exposed to a particulate pollutant, residual oil fly ash (ROFA). Both stimuli caused rapid TP and ROI production in MOs and AMs. However, neither NF-B translocation nor IL-8 gene induction occurred in adhered or ROFA-exposed AMs. Analysis of MAP kinase activation found phosphorylation of Jun amino-terminal kinase (JNK) and p38 in the AMs, but not of extracellular regulated kinase/MAP kinase (ERK/MAPK). AMs stimulated with lipopolysaccharide activated ERK/MAPK, in addition to JNK and p38, and showed translocation of NF-B. In contrast to AMs, MO adhesion or exposure to ROFA particles in suspension rapidly activated p38, JNK, and ERK/MAPK, and activated NF-B binding as well as IL-8 mRNA expression. Pretreatment with the tyrosine kinase inhibitors genistein or herbimycin A before adherence had no effect on transcriptional activation in MOs, whereas adherence and ROFA-induced oxidant generation was inhibited in both MOs and AMs. Taken together, these data indicate that NF-B activation or generalized transcriptional activation of cytokine genes are independent of changes in oxidant stress imposed on phagocytes by adhesion. Furthermore, the data suggest that certain environmental responses in AMs may be uncoupled from activation of NF-B.

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