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

Cryptogenic organizing pneumonia (COP) is a fibrotic process that prim arily involves the alveolar spaces, alveolar ducts, and small conducti ng 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 i s frequently seen in COP. Little is known about the involvement of alv eolar macrophages in the pathogenesis of COP. However, alveolar macrop hages are the principal resident cells in the airways, and they are th ought to play a central role in the fibrotic process by virtue of thei r ability to express and release cytokines such as interleukin-8 (IL-8 ; a neutrophil chemotactic factor) and fibronectin (FN; a fibrogenic m atrix-associated protein). We have quantified the spontaneous gene exp ression of IL-8 and FN by alveolar macrophages from five nonsmoking in dividuals with COP and compared them with 10 normal, healthy volunteer s (five smokers, five nonsmokers). Expression of IL-8 and FN was measu red by a quantitative assay employing reverse transcription of mRNA an d the polymerase chain reaction. Beta-actin mRNA expression was quanti fied as an internal standard, and the expression of FN and IL-8 transc ripts was calculated as a ratio with beta-actin. The mean +/- SEM of t he IL-8/beta-actin ratio in alveolar macrophages from patients with CO P was 0.45 +/- 0.07, which was significantly higher than the level fro m either normal smokers (0.19 +/- 0.02, P = 0.008) or normal nonsmoker s (0.16 +/- 0.01, P = 0.005). The mean +/- SEM of the FN/beta-actin ra tio in alveolar macrophages from patients with COP was 0.39 +/- 0.04, which was significantly higher than the level from either normal smoke rs (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 acti vated in patients with COP They suggest that macrophage-derived IL-8 a nd FN participate in the regulation of the inflammatory and fibrotic p rocesses in the lungs of patients with COP.