We have demonstrated that the activation of peripheral blood monocytes/macrophages plays a central role during acute Kawasaki disease(KD). Electron microscopy showed that peripheral blood CD14+ monocytes/macrophages from patients with acute KD had nuclei with complex shapes, apparent nucleoli and abundant intracytoplasmic granules, some of which were positive for acid phosphatase. The quantity of intracytoplasmic granules was correlated with disease severity. Next, we examined peripheral blood CD14+ monocytes/macrophages using a monoclonal antibody, PM-2K, which recognizes mature macrophages but not monocytes. Approximately 15-20% of peripheral blood CD14+ monocytes/macrophages from KD patients were positive for PM-2K antibody as determined by immunoelectron microscopy. These results suggest that monocytes partly differentiate into macrophages in the peripheral circulation. Recently, it has been reported that the CD14+CD16+ monocyte/macrophage subpopulation plays a more important role in inflammation. We observed an increase in the number of peripheral blood CD14+CD16+monocytes/macrophages with acute KD, which was a positive correlation with C-reactive protein levels, and we observed only the patients with severe bacterial infections had increased this subpopulation during the acute stage among control diseases. We investigated the activation of transcription factor NF-κB for genes that encode the proinflammatory cytokines in CD14+ monocytes/macrophages and CD3+ T cells in peripheral blood by means of Western blot and flow cytometric analyses. NF-κB activation was more increased in CD14+ monocytes/macrophages than in CD3+ T cells in KD patients during the acute stage. The present findings suggest that peripheral blood CD14+ monocytes/macrophages play an important role in cytokine production during acute KD.
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