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 macrophage-like 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 beta-PPT-I mRNA was increased in lipopolysaccharide (LPS)-stimulated U-937 cells. SP-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 neurokinin1 receptor messenger ribonucleic acid, suggesting an autocrine effect of substance P on these cells.
Germonpre
P R
PR
Dept of Respiratory Diseases, University of Ghent, Belgium.
Bullock
G R
GR
Lambrecht
B N
BN
Van De Velde
V
V
Luyten
W H
WH
Joos
G F
GF
Pauwels
R A
RA
D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D017403:In Situ Hybridization; D017493:Leukocyte Common Antigens / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000235:genetics / Q000378:metabolism*; D013183:Sputum / Q000166:cytology*; D013373:Substance P / Q000494:pharmacology; D015320:Tachykinins / Q000235:genetics / Q000378:metabolism; D020298:U937 Cells / Q000187:drug effects / Q000378:metabolism*
D006684:HLA-DR Antigens; D008070:Lipopolysaccharides; D011498:Protein Precursors; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D015320:Tachykinins; C044206:preprotachykinin; D013373:Substance P; D017493:Leukocyte Common Antigens