Adhesion and pollution particle-induced oxidant generation is neither necessary nor sufficient for cytokine induction in human alveolar macrophages

Adhesion of human monocytes (MOs) results in the rapid transcriptional acti vation of cytokine genes that are dependent on nuclear factor (NF)-kappa B, Several pathways leading to activation of NF-kappa B have been described, including those involving reactive oxygen intermediates (ROIs) and members of the mitogen-activated protein (MAP) kinase superfamily, To investigate t he involvement of tyrosine phosphorylation (TP) and oxidant generation in i nterleukin (IL)-8 and GRO messenger RNA induction, MOs and human alveolar m acrophages (AMs) were adhered to plastic or exposed to a particulate pollut ant, residual oil fly ash (ROFA), Both stimuli caused rapid TP and ROI prod uction in MOs and AMs. However. neither NF-kappa B translocation nor IL-8 g ene induction occurred in adhered or ROFA-exposed AMs. Analysis of MAP kina se activation found phosphorylation of Jun amino-terminal kinase (JNK) and p38 in the AMs, but not of extracellular regulated kinase/MAP kinase (ERK/M APK). AMs stimulated with lipopolysaccharide activated ERK/MAPK, in additio n to JNK and p38, and showed translocation of NF-kappa B, In contrast to AM s, MO adhesion or exposure to ROFA particles in suspension rapidly activate d p38, JNK, and ERK/MAPK, and activated NF-kappa 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 activati on in MOs, whereas adherence and ROFA-induced oxidant generation was inhibi ted in both MOs and AMs. Tal;en together, these data indicate that NF-kappa B activation or generalized transcriptional activation of cytokine genes a re independent of changes in oxidant stress imposed on phagocytes by adhesi on. Furthermore, the data suggest that certain environmental responses in A Ms may be uncoupled from activation of NF-kappa B.