Biomedical subjects

L M Teran

Publications and source records attributed to L M Teran.

28 records · Page 2Linked to original sources

PubMed1997

Identification of neutrophil chemotactic factors in bronchoalveolar lavage fluid of asthmatic patients.

BACKGROUND: Although neutrophils have been implicated in bronchial asthma, the mechanism(s) which bring these cells into the airways is poorly understood. OBJECTIVE: To investigate the presence and identity of neutrophil chemotactic factors in bronchoalveolar lavage (BAL) fluid from atopic asthmatic subjects. METHOD: BAL fluid was obtained from 13 subjects (seven asthmatics and six normals), aged 19 to 60 yr, at bronchoscopy. Separation of neutrophil chemotactic activity (NCA) was achieved by FPLC cation exchange chromatography. Fractions were collected and assayed for chemotaxis in multiwell micro-chemotaxes chambers using polycarbonate filters, for the complement peptide C5a/C5a des Arg by radioimmunoassay (RIA) and for interleukin-8 (IL-8) by ELISA. RESULTS: NCA was found in FPLC fractions of BAL samples in four out of seven asthmatics and each of these subjects had at least three similar peaks of NCA. The major peak of NCA was found to contain immunoreactive C5a/C5a des Arg and chemotaxis. In response to this NCA could be blocked by desensitization of the neutrophils with recombinant C5a. Purified serum derived C5a/C5a des Arg was found to have altered chromatographic properties when added to BAL fluid; this suggested that BAL fluid contained proteins which interacted with the C5a/C5a des Arg. Immunoreactive IL-8 (iIL-8) was also detected but its concentration or chemical form was insufficient to induce neutrophil chemotaxis. CONCLUSION: This study demonstrates that bronchial asthmatic lavage fluid contains C5a/ C5a des/Arg and IL-8, together with other as yet unidentified factors which may contribute to neutrophil recruitment in this disease.

Adolescent↗

PubMed1996

Eosinophil recruitment following allergen challenge is associated with the release of the chemokine RANTES into asthmatic airways.

Eosinophil infiltration of the airways in response to allergen exposure is a characteristic of bronchial asthma. However, the mechanisms by which these cells are recruited are poorly understood. We have investigated the presence of eosinophil chemotactic activity (ECA) in bronchoalveolar lavage fluid obtained from allergic asthmatics (n = 6) 4 h after endobronchial allergen challenge. ECA was purified by sequential heparin affinity chromatography and reverse-phase HPLC. A single peak of ECA was detected; SDS-PAGE and Western blot analysis showed that the peak contained a protein of 8 kDa and corresponded to the chemokine RANTES (regulated upon activation, normal T cell expressed and secreted). Consistent with this, the ECA was neutralized by an Ab to RANTES. Measurement of RANTES by ELISA in 10x concentrated bronchoalveolar lavage fluid showed increased levels of this chemokine at the allergen site (median, 187 pg/ml; range, 46-263 pg/ml) in comparison with a saline challenge control site (median, 32.5 pg/ml; range, 11-94 pg/ml), P < 0.005. Furthermore, there was a significant correlation between concentrations of immunoreactive RANTES and the number of eosinophils at the allergen challenge site (r = 0.8; p < 0.001), but not at the saline site (r = 0.2; p = 0.12). These results suggest that RANTES in involved in the recruitment of eosinophils into the asthmatic airways after allergen challenge.

Adult↗

PubMed1996

Cellular and mediator responses twenty-four hours after local endobronchial allergen challenge of asthmatic airways.

The effects of acute allergen exposure on bronchoalveolar lavage cells and mediators and mucosal inflammatory cells were evaluated in 10 subjects with atopic asthma who underwent lavage and biopsy 24 hours after segmental endobronchial allergen challenge. Increased numbers of bronchoalveolar lavage eosinophils were retrieved from the allergen-challenged sites compared with the saline-challenged sites (mean 21.4 vs 1.5 x 10(3) cells/ml; p < 0.02). Numbers of neutrophils and proportions of CD4+, CD8+, CD25+, and HLA-DR+ T cells were similar at the saline- and allergen-challenged sites. In contrast to the bronchoalveolar lavage findings, eosinophil numbers were not increased in the bronchial submucosa or epithelium. There was also no significant difference in neutrophils, mast cells, CD3+, CD4+, or CD8+ T cells in the submucosa after allergen challenge, but the number of activated (CD25+) T lymphocytes in the mucosa did increase after allergen challenge. Allergen challenge did not induce any significant change in endothelial expression of P-selectin, E-selectin, intercellular adhesion molecule-1, or vascular cell adhesion molecule-1. CD11a+ and very late antigen-4+ cell numbers were similar in the saline- and allergen-challenged sites. This study suggests that in patients with very mild asthma, local allergen challenge induces persistent bronchoalveolar lavage eosinophilia, but the recruitment process seems to have diminished or ceased by 24 hours.

Adult↗

PubMed1996

Safety aspects of local endobronchial allergen challenge in asthmatic patients.

Local endobronchial allergen challenge is being increasingly used to investigate the role of allergic inflammation in asthma. However, little information is available about the safety of this procedure and the changes induced in airway physiology. BAL and biopsy were performed at 10 min and at 4 to 6 h, or 24 h after segmental allergen challenge in 49 patients with atopic asthma. Two hours after challenge, FEV1 was reduced from 97.6 +/- 13.9 (mean +/- SD) to 83.4 +/- 21.7% predicted. FEV1 remained reduced at 4 to 6 h (87.7 +/- 20.4%), but it had nearly returned to baseline by 24 h (93.2 +/- 14.0%). When endobronchial challenge was combined with BAL and biopsy, the initial fall in FEV1 was slightly greater (from 101.8 +/- 14.2 to 78.5 +/- 13.6%). Bronchial responsiveness to methacholine was measured in 10 subjects, and it showed a twofold increase 24 h after local challenge and lavage. Significant changes in FEV1 and methacholine PC20 were still detectable 72 h after challenge. Widespread wheezing occurred in 29% of the subjects, but none of the them had to be admitted to hospital. We conclude that local endobronchial allergen challenge, although producing measurable changes in airway physiology, is in general well tolerated and is an acceptable method to investigate airway pathophysiologic processes in patients with mild to moderate asthma.

Adult↗

PubMed1996

Leukocyte recruitment after local endobronchial allergen challenge in asthma. Relationship to procedure and to airway interleukin-8 release.

We have investigated the profile of cellular recruitment into asthmatic airways after allergen and saline exposure and its relationship to interleukin-8 (IL-8) release. Fiberoptic bronchoscopy was used to instill allergen into the middle lobe while the right upper lobe received a sham saline challenge. Bronchoalveolar lavage (BAL) of both sites was performed either 4 or 24 h later. Neutrophil numbers in BAL fluid obtained 4 and 24 h after challenge were 17 and 48 times higher than prechallenge numbers (p < or = 0.001), but there was no statistically significant difference between the numbers of neutrophils at the two sites. In contrast, eosinophil numbers were increased by 6- and 20-fold, respectively, at 4 and 24 h at allergen-challenged as compared with saline-challenged sites (p < 0.005 and p < 0.02, respectively). Baseline concentrations of IL-8 in BAL fluid were undetectable in most cases. Four hours after allergen or saline exposure, BAL fluid IL-8 concentrations were: median, 200 pg/ml; range, 20 to 750 pg/ml and median, 123 pg/ml; range, < 20 to 800 pg/ml, respectively. These declined to 23 pg/ml (range, < 20 to 126 pg/ml) and 43 pg/ml (range < 20 to 130 pg/ml), respectively, 24 h after exposure. There was a significant correlation between neutrophil numbers and IL-8 concentrations 4 h after saline exposure. These findings indicate that neutrophil infiltration is a nonspecific response to the procedure of bronchoscopy and lavage, in contrast to eosinophil recruitment, which is an allergen-specific phenomenon, and it suggests that IL-8 release may be involved in neutrophil recruitment.

Adult↗

PubMed1996