Tachykinin activation of human alveolar macrophages in tobacco smoke and sarcoidosis: A phenotypical and functional study

• Published in: Neuropeptides (Edinburgh) 1996-10, Vol.30 (5), p.456-464
• Main Authors: Brunelleschi, S, Guidotto, S, Viano, I, Fantozzi, R, Pozzi, E, Ghio, P, Albera, C
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Bronchoalveolar Lavage Fluid - chemistry; Bronchoalveolar Lavage Fluid - cytology; Female; Humans; Immunophenotyping; Macrophage Activation - drug effects; Macrophages, Alveolar - drug effects; Macrophages, Alveolar - metabolism; Macrophages, Alveolar - pathology; Male; Medical sciences; Middle Aged; Neurokinin A - analogs & derivatives; Neurokinin A - pharmacology; Peptide Fragments - pharmacology; Peptidyl-Dipeptidase A - analysis; Receptors, Neurokinin-2 - agonists; Respiratory Burst - drug effects; Sarcoidosis, Pulmonary - pathology; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Smoking - pathology; Substance P - pharmacology; Superoxides - metabolism; Tachykinins - pharmacology
• ISSN: 0143-4179; 1532-2785
• DOI: 10.1016/S0143-4179(96)90010-4

Substance P (SP) and neurokinin A (NKA), which exert bronchoconstrictor effects on human airways, are known to interact with inflammatory and immune cells, including monocyte macrophages. We have evaluated the effects of SP, NKA and the NK 2 selective agonist [β-Ala 8]-NKA(4–10) on alveolar macrophages (AM) isolated from 4 healthy smokers and 4 non-smoker active pulmonary sarcoid patients. An accumulation of activated mononuclear phagocytes, as well as elevated angiotensin-converting enzyme (ACE) activity, has been evidenced in both clinical conditions. The phenotype of AMs in the studied subjects was characterized by an elevated expression of CD68+, HLA-DR+ and CD14+, CD14+ being significantly less in sarcoidosis as compared to smokers. SP, NKA and the NK2 selective agonist evoked superoxide anion (O 2 −) production in AMs obtained from sarcoid patients or healthy smokers. While SP acted in a non-dose-dependent manner in both conditions, NKA and [β-Ala 8]-NKA(4–10) evokeda dosedependent respiratory burst (ED 50 = 0.25 and 0.26 nM, respectively) in smokers, but not in sarcoidosis. The more marked phenotypical expression correlated well with the ability of NK 2 receptors to activate AMs in smoker subjects.