Inflammatory cells as source of tachykinin-induced mucus secretion in chronic bronchitis.
Substance P and neurokinin A are regulatory peptides of the tachykinin family that influence many aspects of human airway function in health and diseases such as bronchial asthma or chronic obstructive pulmonary disease (COPD). Tachykinin-induced mucus secretion has been regarded as sensory nerve-dependent so far. We studied the distribution of tachykinin-mRNA and -peptide and its relation to NK-1 subtype-positive cells in human airway glands to assess if tachykinins may also be expressed in inflammatory cells. RT-PCR demonstrated the expression of tachykinin- and NK-1-mRNA in human airway tissues. In situ hybridisation resulted in preprotachykinin (PPT)-A mRNA-signal detection in inflammatory cells which were in close contact to myoepithelial cells of airway glands. NK-1 immunoreactivity was found in myoepithelial cells which were in direct contact to the PPT-A mRNA and tachykinin-positive cells. The present data directly demonstrate the presence of both PPT-A mRNA and tachykinin immunoreactivity in inflammatory airway cells which are in direct contact to NK-1 receptor positive glandular myoepithelium. Our findings indicate that besides neurally released tachykinins, also inflammatory cell-derived tachykinins may lead to glandular secretion via NK-1 receptor stimulation. This points to a major second source of these proinflammatory mediators in chronic inflammatory airway diseases such as COPD or asthma.
Springer
Jochen
J
Otto-Heubner-Centre, Pneumology and Immunology, Charité School of Medicine, Free University and Humboldt-University, Augustenburger Platz 1 OR-1, D-13353 Berlin, Germany.
Groneberg
David A
DA
Pregla
Reinhard
R
Fischer
Axel
A
D029481:Bronchitis, Chronic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D009093:Mucus / Q000378:metabolism*; D011014:Pneumonia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000235:genetics / Q000378:metabolism; D012137:Respiratory System / Q000378:metabolism / Q000473:pathology; D015320:Tachykinins / Q000235:genetics / Q000378:metabolism*
D011498:Protein Precursors; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D015320:Tachykinins; C044206:preprotachykinin