CRYPTOGENIC ORGANIZING PNEUMONIA - INCREASED EXPRESSION OF INTERLEUKIN-8 AND FIBRONECTIN GENES BY ALVEOLAR MACROPHAGES

Cryptogenic organizing pneumonia (COP) is a fibrotic process that primarily involves the alveolar spaces, alveolar ducts, and small conducting airways. The pathogenesis is not understood. Recent histopathologic studies have shown that during the cellular phase of COP, fibronectin deposits are present in the lung. Moreover, a neutrophil alveolitis is frequently seen in COP. Little is known about the involvement of alveolar macrophages in the pathogenesis of COP. However, alveolar macrophages are the principal resident cells in the airways, and they are thought to play a central role in the fibrotic process by virtue of their ability to express and release cytokines such as interleukin-8 (IL-8; a neutrophil chemotactic factor) and fibronectin (FN; a fibrogenic matrix-associated protein). We have quantified the spontaneous gene expression of IL-8 and FN by alveolar macrophages from five nonsmoking individuals with COP and compared them with 10 normal, healthy volunteers (five smokers, five nonsmokers). Expression of IL-8 and FN was measured by a quantitative assay employing reverse transcription of mRNA and the polymerase chain reaction. Beta-actin mRNA expression was quantified as an internal standard, and the expression of FN and IL-8 transcripts was calculated as a ratio with beta-actin. The mean +/- SEM of the IL-8/beta-actin ratio in alveolar macrophages from patients with COP was 0.45 +/- 0.07, which was significantly higher than the level from either normal smokers (0.19 +/- 0.02, P = 0.008) or normal nonsmokers (0.16 +/- 0.01, P = 0.005). The mean +/- SEM of the FN/beta-actin ratio in alveolar macrophages from patients with COP was 0.39 +/- 0.04, which was significantly higher than the level from either normal smokers (0.28 +/- 0.01, P = 0.03) or normal nonsmokers (0.15 +/- 0.03, P = 0.02). These data show that alveolar macrophages are functionally activated in patients with COP They suggest that macrophage-derived IL-8 and FN participate in the regulation of the inflammatory and fibrotic processes in the lungs of patients with COP.