Chemokine CC-ligand 5 production and eosinophil activation into the upper airways of aspirin-sensitive patients.

BACKGROUND: Airway eosinophilia is a hallmark of aspirin-sensitive asthma/rhinitis. OBJECTIVE: We have investigated chemokine CC-ligand 5 (CCL5) production and its association with eosinophil activation in the upper airways of aspirin-sensitive patients both in vivo and in vitro. METHODS: Twenty aspirin-sensitive asthma/rhinosinusitis patients, 18 atopic-tolerant asthma/rhinosinusitis patients and 15 healthy control subjects took part in the study. All subjects were challenged with saline and lysine-acetylsalicylic acid (L-asa) on separate occasions. Nasal lavages were obtained at baseline and 120 min after challenge and analysed for mediators' release. RESULTS: When compared with control subjects, the baseline levels of CCL5 were significantly increased in both sensitive and tolerant patients (there was no significant difference in CCL5 concentrations between these two groups, P>0.05). However, L-asa nasal challenge induced significantly increased levels of CCL5 in the sensitive patients but not in the tolerant subjects (median: 380 vs. 140 pg/mL, P<0.0001). Similarly, the concentrations of both eosinophil cationic protein (ECP) and cysteinil leukotriene (cys-LTs) were increased significantly in the aspirin-sensitive but not in the tolerant patients. There was a trend towards a significant correlation between CCL5 and ECP concentrations in the sensitive patients following L-ASA challenge. On incubation with aspirin, nasal tissue derived from aspirin-sensitive but not that derived from tolerant subjects released increased CCL5 levels in culture. As determined by immunohistochemistry, CCL5 was predominantly localized to the nasal airway epithelium. CONCLUSION: Altogether, these findings suggest that CCL5 is released in aspirin-sensitive asthma/rhinosinusitis.

Role of monocyte chemotactic protein-3 and -4 in children with virus exacerbation of asthma.

Macrophages play a crucial role in respiratory viral infections. However, the mechanisms by which these cells are recruited locally are not fully understood. The current authors studied the role of the chemokines monocyte chemotactic protein (MCP)-1, -2, -3 and -4 on monocyte/macrophage recruitment during respiratory viral infections. Levels of these chemokines were investigated in nasal aspirates from 6-12-yr-old children suffering from respiratory viral infections, caused by rhinoviruses, influenza viruses, parainfluenza viruses, adenoviruses and respiratory syncytial virus. MCP-3 and -4 were significantly higher in samples derived from virus-infected children compared with samples from the same children when they had been asymptomatic. Concentrations of both chemokines were found to significantly correlate with the number of recruited nasal macrophages. Chemotaxis assays showed that purified MCP-3 and -4 from nasal aspirates showed biological activity in vitro. There were no significant differences in MCP-1 and -2 levels between both groups. The present data indicates that monocyte chemotactic protein-3 and -4 may have an important role in macrophage recruitment in children with proven upper respiratory viral infections. These chemokines could be potential targets for therapeutic intervention in respiratory viral infections.

CC chemokine ligand 1 is released into the airways of atopic asthmatics.

CC chemokine ligand (CCL)1/I-309 is a potent attractant for T-helper cell type 2 lymphocytes. The present study investigates whether this cytokine is released in the bronchoalveolar fluid (BALF) of asthmatic patients. Measurements of CCL1 using ELISA showed that levels of this cytokine were significantly elevated in BALF from asthmatics compared with normals (median (range) 193 (120-449) pg.mL(-1) versus 30 (21-55) pg.mL(-1)). Differential cell counts in BALF showed that either lymphocyte or eosinophil numbers were elevated in asthmatic compared with normal subjects (10.8 x 10(3).mL(-1) versus 1.0 x 10(3).mL(-1) and 1.7 x 10(3).mL(-1) versus 0.2 x 10(3).mL(-1), respectively). There was a trend towards a significant correlation between CCL1 levels and lymphocyte numbers in BALF. Separation of BALF using sequential CCL1 affinity column and reverse-phase high-performance liquid chromatography allowed detection of biologically active CCL1. Using immunohistochemistry, CCL1 immunoreactivity was localised predominantly to the airway epithelium. Interestingly, there was a significant correlation between CC chemokine ligand 1 levels and epithelial cell numbers in bronchoalveolar lavage fluid and between these cells and lymphocyte numbers. Moreover, interleukin-4, interleukin-13 and interferon-gamma stimulated primary bronchial airway epithelial cells to release CC chemokine ligand 1. These findings suggest that CC chemokine ligand 1 may play a role in lymphocyte recruitment in bronchial asthma.