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

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 NK₂ selective agonist [β-Ala⁸]-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 (O₂^-) 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-Ala⁸]-NKA(4-10) evoked a dose-dependent respiratory burst (ED₅₀ = 0.25 and 0.26 nM, respectively) in smokers, but not in sarcoidosis. The more marked phenotypical expression correlated well with the ability of NK₂ receptors to activate AMs in smoker subjects.