Effect of clarithromycin on the cell profile of bronchoalveolar lavage fluid in mice with neutrophil-predominant lung disease Efeito da claritromicina na celularidade do lavado broncoalveolar em camundongos com doença pulmonar neutrofílica induzida

OBJECTIVE: Macrolide antibiotics have anti-inflammatory properties in lung diseases. The aim of this study was to investigate the effect of clarithromycin in pulmonary cellular inflammatory response in mice. METHOD: Eight adult Swiss mice were studied. All animals received an intranasal challenge (80 µL) with dead Pseudomonas aeruginosa (1.0 x 10(12) CFU/mL). Bronchoalveolar lavage was performed 2 days later, with total cell count and differential cell analysis. The study group (n = 4) received clarithromycin treatment (50 mg/kg/day, intraperitoneal) for 5 days. Treatment was initiated 2 days before intranasal challenge. RESULTS: There was no significant difference in total cell count between the groups (mean: 2.0 x 10(6) and 1.3 x 10(6), respectively). In both groups, there was a predominance of neutrophils. However, the study group had a higher percentage of lymphocytes in the bronchoalveolar lavage than the control group (median of 19% vs 2.5%, P = .029). CONCLUSION: Clarithromycin alters the cytological pattern of bronchoalveolar lavage of Swiss mice with neutrophil pulmonary inflammation, significantly increasing the percentage of lymphocytes.<br>OBJETIVO: Os antibióticos macrolídeos podem apresentar um efeito antiinflamatório em doenças pulmonares. O objetivo deste estudo é investigar o efeito da claritromicina na resposta inflamatória celular pulmonar em camundongos Swiss. MÉTODO: Foram utilizados 8 camundongos Swiss adultos (6-8 semanas). Todos os animais receberam um desafio intranasal (80 µL) com Pseudomonas aeruginosa mortas (1 x 10(12) UFC/mL). Dois dias após o desafio, foi realizado lavado broncoalveolar (LBA) com contagem total de células (CTC) e exame citológico diferencial. O grupo em estudo (n=4) recebeu tratamento com claritromicina (50mg/kg/dia, intraperitoneal) por 5 dias, sendo iniciado o tratamento 2 dias antes do desafio intranasal. O grupo controle (n=4) não recebeu tratamento com claritromicina. RESULTADOS: Não houve diferença significativa na CTC entre os grupos (média de 2x10(6) e 1,3x10(6), respectivamente). Em ambos os grupos, houve predomínio absoluto de neutrófilos. Contudo, o grupo tratado com claritromicina, apresentou um número percentual significativamente maior de linfócitos no LBA (mediana de 2,5% vs 19%, p=0,029). CONCLUSÃO: O uso de claritromicina altera o exame citológico diferencial do lavado bronco-alveolar de camundongos Swiss com inflamação pulmonar neutrofílica, aumentando significativamente o número percentual de linfócitos

Characterization of CD44 expressed on alveolar macrophages in patients with diffuse panbronchiolitis

Interleukin (IL)-8 may play an important role in neutrophil infiltration in the airways of patients with diffuse panbronchiolitis (DPB). Furthermore, alveolar macrophages could produce IL-8 subsequent to CD44-hyaluronic acid (HA) interaction. The purpose of this study was to evaluate the contribution of CD44 expressed on alveolar macrophages to the pathogenesis of DPB. We examined the concentration of soluble CD44 (sCD44) in bronchoalveolar lavage fluid (BALF) and CD44 expression on macrophages in BALF from patients with DPB before and after low-dose, long-term macrolide therapy. We also assessed the HA-binding ability of alveolar macrophages as a functional analysis of the CD44 molecule. The sCD44 concentration in BALF was significantly lower in patients with DPB than in healthy volunteers. Percentages of alveolar macrophages expressing low CD44 (CD44 low+) and HA-nonbinding alveolar macrophages were higher in patients with DPB compared with healthy volunteers. Furthermore, macrolide therapy normalized CD44 expression and HA-binding ability of macrophages in BALF from DPB patients. Our findings suggest that alveolar macrophage dysfunction could result from abnormalities of CD44 expression in patients with DPB and that these events could contribute to the pathogenesis of DPB