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 bronchoconstricto r effects on human airways, are known to interact with inflammatory an d immune cells, including monocyte macrophages. We have evaluated the effects of SP, NKA and the NK2 selective agonist [beta-Ala(8)]-NKA(4-1 0) on alveolar macrophages (AM) isolated from 4 healthy smokers and 4 non-smoker active pulmonary sarcoid patients, An accumulation of activ ated mononuclear phagocytes, as well as elevated angiotensin-convertin g enzyme (ACE) activity, has been evidenced in both clinical condition s, The phenotype of AMs in ?he studied subjects was characterized by a n elevated expression of CD68+, HLA-DR+ and CD14+, CD14+ being signifi cantly 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 [beta-Ala(8)]-N KA(4-10) evoked a dose-dependent respiratory burst (ED(50) = 0.25 and 0.28 nM, respectively) in smokers, but not in sarcoidosis. The more ma rked phenotypical expression correlated well with the ability of NK2 r eceptors to activate AMs in smoker subjects.