Brunelleschi S, Guidotto S, Viano I, Fantozzi R, Pozzi E, Ghio P, Albera C
Department of Medical Sciences, University of Turin, Novara, Italy.
Neuropeptides. 1996 Oct;30(5):456-64. 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 NK2 selective agonist [beta-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 [beta-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.
P物质（SP）和神经激肽A（NKA）对人类气道有支气管收缩作用，已知它们可与包括单核巨噬细胞在内的炎症和免疫细胞相互作用。我们评估了SP、NKA和NK2选择性激动剂[β-丙氨酸8]-NKA(4 - 10)对从4名健康吸烟者和4名非吸烟活动性肺结节病患者分离的肺泡巨噬细胞（AM）的影响。在这两种临床情况下均已证实存在活化的单核吞噬细胞积聚以及血管紧张素转换酶（ACE）活性升高。研究对象中AM的表型特征为CD68 +、HLA - DR +和CD14 +表达升高，与吸烟者相比，结节病患者中CD14 +明显较少。SP、NKA和NK2选择性激动剂可诱导结节病患者或健康吸烟者的AM产生超氧阴离子（O2-）。虽然SP在两种情况下均以非剂量依赖性方式起作用，但NKA和[β-丙氨酸8]-NKA(4 - 10)在吸烟者中可诱导剂量依赖性呼吸爆发（ED50分别为0.25和0.26 nM），而在结节病患者中则不然。更明显的表型表达与NK2受体激活吸烟者中AM的能力密切相关。
