CC and C chemokine expression in pulmonary sarcoidosis. M. Petrek, V. Kolek, J. Szotkowská, R.M.du Bois. #ERS Journals Ltd 2002. ABSTRACT: The chemokines RANTES (regulated on activation, T-cell expressed and secreted; CC chemokine ligand (CCL)-5) and monocyte inflammatory protein (MIP)-1a (CCL-3) have been implicated in the development of alveolitis in pulmonary sarcoidosis. The novel C chemokine single cysteine motif (SCM)-1a (XCL-1) and the CC chemokine monocyte chemoattractant protein (MCP)-1 (CCL-2) are also mononuclear-cell attractants and represent alternative candidate mediators of alveolitis. Therefore, the expression of MCP-1 and SCM-1a was investigated together with the expression of RANTES and MIP-1a in bronchoalveolar lavage fluid (BALF) from control subjects and patients with sarcoidosis. The relationship between chemokine expression and sarcoidosis clinical course was also explored.Messenger ribonucleic acid (mRNA) expression for all four chemokines was determined by semiquantitative reverse transcriptase-polymerase chain reaction of RNA extracted from unseparated bronchoalveolar cells (17 patients, 12 controls). RANTES, MIP-1a and MCP-1 proteins were measured by enzyme-linked immunosobent assay of unconcentrated BALF (60 patients, 17 controls).MCP-1, and namely RANTES and SCM-1a mRNA expression was upregulated in sarcoidosis, particularly in patients with more advanced disease. RANTES, and namely MCP-1 concentrations were elevated in BALF samples obtained from patients; MCP-1 levels were most increased in patients with chest radiographic stage 2 disease and also in patients with persistent and recurrent disease.In conclusion, chemokines monocyte chemotactive protein-1 and single cysteine motif-1a are, in addition to RANTES, associated with the development of alveolitis in sarcoidosis and their expression parallels the disease course.

In this study, messenger RNA (mRNA) expression for novel T lymphocyte chemoattractants, leukotactin-1, macrophage inflammatory protein (MIP)-3 alpha and MIP-3 beta was investigated in bronchoalveolar lavage fluid (BALF) cells from patients with sarcoidosis, a T cell-mediated disease with typical CD4+ lymphocyte alveolitis. Of these three chemokines, only MIP-3 beta mRNA was upregulated in sarcoidosis, and therefore, protein levels of this chemokine, its pharmacologic regulation, and association with disease clinical course were explored. MIP-3 beta protein concentrations were elevated in BALF from sarcoid patients compared with control subjects (p = 0.001) and in patients with chest X-ray stage II chemokine protein levels were increased compared with stage I (p = 0.003). MIP-3 beta protein was associated predominantly with alveolar macrophages and correlated with BALF lymphocytes and T cell subsets. mRNA expression for the MIP-3 beta receptor, CC chemokine receptor 7, was increased in sarcoidosis and correlated with MIP-3 beta protein levels. MIP-3 beta mRNA and protein expression in BALF cells was suppressed by dexamethasone and cyclosporine A in vitro. In conclusion, MIP-3 beta is implicated in T lymphocyte recruitment in sarcoidosis, is associated with disease progression, and is downregulated by drugs used for sarcoidosis treatment. This novel chemokine, therefore, represents a candidate for studies of sarcoidosis pathobiologic mechanisms.

BACKGROUND: Chemokine-driven migration of inflammatory cells has been implicated in the pathogenesis of atherosclerotic conditions including peripheral arterial disease (PAD). Monocyte chemoattractant protein-1 (MCP-1) is elevated in patients with coronary artery disease and in hypertensive patients. This study therefore investigated MCP-1 in patients with PAD. METHODS: Serum MCP-1 was determined by enzyme-linked immunosorbent assay in 36 healthy, control subjects and in 19 patients with PAD. Statistical analysis utilised the Mann-Whitney test and Spearman correlation (p < 0.05). RESULTS: MCP-1 (pg/ml) was increased in patients compared with in controls (mean+/-standard error of the mean: PAD group, 748+/-60; control group, 459+/-27; p=0.0001). MCP-1 levels tended to decrease with progressing disease. From atherosclerosis risk factors, diabetes inclined to increase MCP-1 levels; hypertension had no effect. Serum MCP-1 correlated with cholesterol, triglycerides, low-density lipoprotein but not high-density lipoprotein. Conclusion: Elevation of MCP-1 in the circulation of PAD patients shown in the present pilot study implicates this CC chemokine ligand 2 in inflammatory processes contributing to PAD clinical symptomatology. Further investigations are necessary to evaluate whether MCP-1 can be used as a potential marker of peripheral arterial disease follow-up and/or prognosis.

BACKGROUND. Although several studies have demonstrated an association between infection with Chlamydia pneumoniae and asthma, these were mainly limited to exacerbation of symptoms in adults with known asthma OBJECTIVE. We investigated the role of C. pneumoniae infection in l49 atopic children with chronic cough and asthma, comparing them with 241 control non-atopic subjects presenting at Olomouc hospital between 1999 and 2003 with non-specific symptoms (temperature above normal (subfebrile), abdominal pain, arthralgia, and other symptoms.METHODS. The levels of C. pneumoniae-specific antibodies were measured using Chlamydien-rELISA kits (Medac, Hamburg, Germany).RESULTS. In a group of 83 atopic children with chronic cough, IgM and IgG antibodies to C. pneumoniae were demonstrated in 20 children (24 %). Among children with bronchial asthma, positive antibody was present in 29 children (44 %; /p = 0,052/); of this number, 24 (36 %; /p = 0,06/) had IgM and IgG antibodies while 5 children (8 %) had IgA and IgG antibodies against C. pneumoniae. A group of non-atopic children with non-specific symptoms included 38 children (16 %) with antibody positivity; 27 children (11 %) with IgM and IgG antibodies and 11 children (5 %) with IgA and IgG antibodies against C. pneumoniae.CONCLUSIONS. Asthma in children was associated with elevated levels of IgM and IgG antibodies to C. pneumoniae.

To explore the use of oscillometry as a measure of airway responsiveness, 69 asthmatic children underwent histamine and methacholine bronchoprovocation using dosimeter-MedicAid (Jaeger Co.; Germany) and DeVilbiss nebulizers (DeVilbiss, Bornemouth; England). The mean increase in R5 resistance in challenge testing measured after methacholine with the dosimeter-MedicAid nebulizer was 77.14% compared with 65.05% using histamine. Using the dosimeter-DeVilbiss nebulizer, the mean increases in R5 resistance following methacholine and histamine testing were 57.50% and 59.36%, respectively. The resistance R5 over R20 significantly correlated with forced expiratory volume in 1 second (FEV1). The MedicAid produced a more aggressive challenge than the DeVilbliss nebulizer. Oscillometry can be used to monitor the level of airway hyperresponsiveness following bronchoprovocation tests.

The reactions of five dyes of the alizarin green series with vanadates in the presence of cetyltrimethylammonium (CTA+, S) or Ag(1,10-phen)2+ cations were studied. At lower concentrations of tenside than the cmc value, defined ternary complexes with composition VL2S4 or VL2S6 or quaternary complexes VL3[Ag(1,10-phen)2]9 are formed in solution. The equilibrium constants of the studied complexation reactions were determined and a method for the photometric and chelometric determination of vanadium were proposed.