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

Three types of tachykinin receptors, NK(1), NK(2)and NK(3), have been described to preferentially interact with substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) respectively. Experimental evidence indicates that SP and NKA modulate the activity of inflammatory and immune cells, including mononuclear ones, and points to their involvement in lung pathophysiology. We previously reported that NK(1)and NK(2)receptors are present on monocytes (MO) isolated from healthy donors or rheumatoid patients - a greater sensitivity to NK(2)receptor stimulation was observed in the latter condition. This study evaluated the effects of SP and NKA, as well as NK(1)and NK(2)selective agonists and antagonists, on MO obtained from healthy volunteers, healthy smokers or patients with interstitial lung diseases (e.g. sarcoidosis and idiopathic pulmonary fibrosis). Superoxide anion (O(2)(-)) production was chosen 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 10 627, respectively). When selective NK(1)and NK(2)agonists were used, [Sar(9)Met(O(2))(11)]SP, a selective NK(1)agonist, induced a more than doubled O(2)production in MO obtained from patients with interstitial lung diseases as compared to healthy volunteers, whereas MO isolated from healthy volunteers were more sensitive to NK(2)receptor stimulation.

p53 expression in cultured blood human monocytes infected with mycobacterial strains.

BACKGROUND: An upregulation of the cell-cycle associated proteins p53 and p21/Waf1/Cip1 induced by mycobacteria was previously reported. We aimed to evaluate the expression of such proteins in peripheral blood human monocyte cultures infected with strains of different mycobacterial pathogens. METHODS: The study relied on the immunocytochemical determination of p53, p21/Waf1/Cipl, bcl-2 and on the Tunel detection of apoptosis in monocytes populations cultured on four-welled chamber slides (10(6) cells/well) infected with Mycobacterium tuberculosis, M. bovis and M. avium for four consecutive days (mycobacterium/monocyte ratio 10:1). The results were expressed as mean values and SD of the percentages of stainings recorded in five fields per slide. RESULTS: The statistical analysis with Fischer test demostrated that at most sampling times the p53 and p21/Waf1/Cip1 expression and the apoptosis index were significantly higher in M. tuberculosis infected cultures than in controls (p<0.05). The M. bovis related picture diverged from the previous one for a lower p53 expression (p<0.05) at all sampling times. The M. avium infected culture values did not diverge significantly from the controls. CONCLUSIONS: The p53 and p21/Wafl/Cipl upregulation is compatible with both host defense strategies and pathogen strategies (safeguard of intracellular sanctuaries). The discrepancies among different cultures suggest a direct relationship between p53 activation and mycobacterial ability to enter host cells.

Radiological aspects of diffuse alveolar haemorrhage.

PURPOSE: This paper describes chest X-ray (CXR) and computed tomography (CT) findings of diffuse alveolar haemorrhage (DAH). MATERIALS AND METHODS: We retrospectively reviewed 23 episodes of DAH in 20 patients, 17 of known aetiology and three of unknown aetiology. All cases were studied by CXR and 15 also by CT. Parenchymal consolidations and ground-glass opacities were evaluated after dividing each lung into three regions (upper, middle, lower) for a total of six zones. RESULTS: Consolidations or ground-glass opacities were identified on CXR in 16/20 patients, mainly in the middle fields (73%). In 4/20 patients, all with Wegener's granulomatosis, CXR was negative or demonstrated only nodular opacities; in two of these cases, CT revealed ground-glass opacities. A complete follow-up was available for ten patients: initially, they showed consolidation opacities in 36/60 zones, which persisted in 16/60 after 7 days and in 11/60 after 15 days. Conversely, ground-glass opacities increased after 7 days owing to the partial regression of consolidation opacities, and they markedly diminished after 15 days. CONCLUSIONS: DAH is radiologically characterised by a nonspecific alveolar-filling pattern. Diagnosis or suspicion of DAH needs to be supported by the evidence of haemoptysis and/or rapid-onset anaemia. CT is superior in detecting ground-glass opacities and is required in cases of suspected DAH with normal CXR findings.