Expression of RANTES by Bronchoalveolar Lavage Cells in Nonsmoking Patients with Interstitial Lung Diseases

Abstract

Emphasis has recently been placed on the roles of chemotactic cytokines called chemokines to explain the accumulation of inflammatory cells in the lung that may precede or accompany pulmonary fibrosis in interstitial lung diseases. We hypothesized that RANTES, a member of the C-C chemokines, is one such chemokine. Bronchoalveolar lavage was done in 20 patients with sarcoidosis, 10 patients with interstitial pneumonia associated with collagen vascular disease (CVD-IP), 10 patients with idiopathic pulmonary fibrosis (IPF), and eight healthy volunteers (HV), all of whom were never-smokers. We semiquantitated the spontaneous RANTES mRNA expression by a competitive reverse transcription-polymerase chain reaction (RT-PCR) technique, and measured the levels of RANTES protein by enzyme-linked immunosorbent assay. In all disease groups the expression of RANTES mRNA by bronchoalveolar lavage fluid (BALF) cells and the levels of RANTES protein in BALF were significantly increased compared with those in HV. Patients with sarcoidosis and CVD-IP had a significant positive correlation between the expression of RANTES mRNA by BALF cells and BALF lymphocytosis. The amounts of RANTES mRNA expressed by peripheral blood mononuclear cells and the levels of RANTES protein in serum did not differ among all study groups. Our study demonstrates the adaptability of a semiquantitative RT-PCR method for determining cytokine mRNA expression in vivo. Our results suggest that RANTES may be one of the chemokines that are involved in the mechanism for the accumulation of inflammatory cells in the lung of some distinct interstitial lung diseases.

CC and C chemokine expression in pulmonary sarcoidosis

“…The complexity of the translation process, and the presence of further modifying factors such as storage of the protein or its possible intracellular degradation, may cause a less than straightforward relationship between intracellular mRNA and protein in the BAL fluid. Despite the above constraints, it is important that the direction of changes was the same at both (protein and mRNA) levels and it was in agreement with previous reports [20][21][22]24].…”

Inflammatory Profile and Response to Anti-Tumor Necrosis Factor Therapy in Patients with Chronic Pulmonary Sarcoidosis

“…MCP-1 has been the chemokine most commonly reported to be overexpressed in sarcoidosis, with reports of increased expression in the airways (6,10,11,16,21) and systemically in serum (9,11,21). RANTES (10,14,17) and ENA-78 (22) were reported to have increased expression in the airways in sarcoidosis; we report here an elevation in serum. IL-8, a neutrophil chemoattractant, was reported to be elevated in the airways (6) and in plasma (4) and was found to be inversely correlated with FVC (23) in sarcoidosis patients.…”

Pivotal Role of CCR1-Positive Leukocytes in Bleomycin- Induced Lung Fibrosis in Mice

“…Second, neutralization of CCR1 would initially lead to a decrease of the infiltration and activation in the CCR1-expressing key cells, such as alveolar macrophages (Fig. 3c), which are the potentially important source of cytokines and chemokines, including TNF-␣, MIP-1␣, RANTES, and MCP-1/JE (1,4,8,9,11,12). Anti-CCR1 Ab reduced the alveolar macrophages in number by 38% (Fig.…”

“…Furthermore, analyses of bronchoalveolar lavage (BAL) and open-lung biopsies from patients with idiopathic pulmonary fibrosis have demonstrated elevated levels of MIP-1␣, RANTES, and MCP-1 compared with that of healthy volunteers (11)(12)(13). A CC chemokine, MIP-1␣, promotes leukocyte accumulation and activation, leading to fibrosis.…”