CHANGES IN PKC ISOFORMS IN HUMAN ALVEOLAR MACROPHAGES COMPARED WITH BLOOD MONOCYTES

Alveolar macrophages play an important role in host defense and in oth er types of inflammatory processes in the lung. These cells exhibit ma ny alterations in function compared with their precursor cells, blood monocytes. To evaluate a potential mechanism for these differences in function, we evaluated expression of protein kinase C (PKC) isoforms. We found an increase in Ca2+-dependent PKC isoforms in monocytes compa red with alveolar macrophages. We also found differential expression o f the Ca2+-independent isoforms in alveolar macrophages compared with monocytes. One consequence of the activation of PKC can be increased e xpression of mitogen-activated protein (MAP) kinase pathways. Therefor e, we also evaluated activation of the MAP kinase extracellular signal -regulated kinase (ERK) 2 by the phorbol ester phorbol 12-myristate 13 -acetate (PMA). PMA activated ERK2 kinase in both alveolar macrophages and monocytes; however, monocytes consistently showed a significantly greater activation of ERK2 kinase by PMA compared with alveolar macro phages. Another known consequence of the activation of PKC and subsequ ent activation of ERK kinase is activation of the transcription factor activator protein-1 (AP-1). We evaluated the activation of AP-1 by PM A in both monocytes and macrophages. We found very little detectable a ctivation of AP-1, as assessed in a gel shift assay, in alveolar macro phages, whereas monocytes showed a substantial activation of AP-1 by P MA. These studies show that the differential expression of PKC isoform s in alveolar macrophages and blood monocytes is associated with impor tant functional alterations in the cells.