Presence of substance P and neurokinin 1 receptors in human sputum macrophages and U-937 cells

Tachykinins such as substance P (SP) may be involved in the pathogenesis of inflammatory airway diseases such as asthma, This study investigated the presence of SP and its receptor in the differentiated macrophagelike U-937 cell Line and in macrophages from sputum induced in healthy subjects (n=8). In situ hybridization with digoxigenin-labelled sense and antisense complementary ribonucleic acid (cRNA) probes was used to determine the expression of SP and its receptor (neurokinin (NK)(1) receptor). SP-immunoreactive material was detected using a rabbit anti-SP antiserum and the alkaline phosphatase anti-alkaline phosphatase technique. beta-preprotachykinin (PPT)-I messenger ribonucleic acid (mRNA) encoding SP, was detected using in situ hybridization in differentiated U-937 cells as well as in CD45+ human leukocyte antigen (HLA) DR+ sputum macrophages. The expression of the PPT-I mRNA was increased in lipopolysaccharide (LPS)-stimulated U-937 cells. beta-immunoreactive material was found in differentiated U-937 cells and in CD68+ sputum macrophages. NK1 receptor mRNA was detected in differentiated U-937 cells and sputum macrophages. Incubation of U-937 cells with SP considerably increased the expression of NK1 receptor mRNA. This study demonstrates that human monocytes/macrophages express substance P and that this expression is upregulated by lipopolysacharide. Human monocytes/macrophages also express neurokinin(1) receptor messenger ribonucleic acid, suggesting an autocrine effect of substance P on these cells.