Tachykinin activation of human monocytes from patients with interstitial lung disease, healthy smokers or healthy volunteers

'Three types of tachykinin receptors, NK1, NK2 and NK3, have been described to preferentially interact with substance P (SP), neurokinin A (NKA) and n eurokinin B (NKB) respectively. Experimental evidence indicates that SP and NKA modulate the activity of inflammatory and immune cells, including mono nuclear ones, and points to their involvement in lung pathophysiology. We p reviously reported that NK1 and NK2 receptors are present on monocytes (MO) isolated from healthy donors or rheumatoid patients - a greater sensitivit y to NK2 receptor stimulation was observed in the latter condition. This st udy evaluated the effects of SP and NKA, as well as NK1 and NK2 selective a gonists and antagonists, on MO obtained from healthy volunteers, healthy sm okers or patients with interstitial lung diseases (e.g. sarcoidosis and idi opathic pulmonary fibrosis). Superoxide anion (O-2(-)) production was chose n as a parameter of cell activation. SP and NKA dose-dependently evoked O-2 (-) production from MO in all the conditions evaluated, their effects being competitively antagonized by selective antagonists (CP 96 345 and MEN 10 6 27, respectively). When selective NK1 and NK2 agonists were used, [Sar (9)M et(O-2)(11)]SP, a selective NK1 agonist, induced a more than doubled O-2 pr oduction in MO obtained from patients with interstitial lung diseases as co mpared to healthy volunteers, whereas MO isolated from healthy volunteers w ere more sensitive to NK2 receptor stimulation. (C) 2000 Harcourt Publisher s Ltd.