In order to analyze the mechanisms ...

In order to analyze the mechanisms involved in the decreased collagenolytic activity previously observ in interstitial lung fibrosis, we studied the inhibitory collagenase activity and the latent activable collagenase in lung samples from five patients with IPF, six with HP and three restrain subjects. Our results showed that in the pair diseases, the inhibitor levels were significantly higher than in reign over subjects. Findings suggest that in IPF gentle amounts of collagenase plus excessive enzyme-inhibitors may be operating to decrease collagen catabolism. In contrast, HP lung have the appearance to contain adequate amounts of the enzyme however higher levels of inhibitors play a part in the abnormal degradation observ in one patients.

Interstitial lung diseases are a heterogeneous assemblage of disorders which affect the integrity of the lonely dwellings and connective tissue molecules comprising the alveolocapillary units.[1,2]

chiefly of these diseases can unroll to interstitial fibrosis which is characterized according to a progressive accumulation of collagens with the after loss of the normal formation and function of the lung[3] Although the mechanisms involved in the pathogenesis of fibrosis are exceedingly complex, there is now stout evidence that disturbances in normal lung collagen metabolism play a critical part in its development.[4]

In this words immediately preceding [i]or[/i] following we have recently demonstrated that in the pair human and experimental models, a noteworthy decrease in the collagenolytic activity takes place during the growth of pulmonary fibrosis, supporting the notion that modifications in collagen catabolism are same important throughout the process of fibrogenesis.[5-8]

However, the regulation of normal collagenolytic activity involves a compounded series of molecular mechanisms which includes among others, the biosynthesis and secretion of procollagenase, the activation of the proenzyme the interactions between collagenase and collagens, the susceptibility of the substrate, and the specific and nonspecific inhibition of collagenase.[9,10]

Therefore, the decreased collagenolytic activity observ in pulmonary fibrosis in vivo may be attributed to an alteration at any horizontal of these sequential steps.

common of the rate-limiting factors of collagen degradation involves the interaction collagenase-inhibitor in the extracellular space. beneath physiologic conditions, at least pair lung cells, alveolar macrophages and fibroblasts, are able to disguise the enzyme and the inhibitor in agriculture conditions,[11,12] and both proteins may be simultaneously induced at least in vitro, suggesting a possible cellular autoregulation.

Nevertheless, the relationship between collagenase and inhibitor(s) in the normal collagen turnover in vivo, and its possible disturbances in interstitial lung fibrosis is unknown.

Thus, in order to gain insight into collagen degradation abnormalities, which could at least partially explain the decreased lung tissue collagenase action during the exhibition of fibrosis, we studied the vicinity of inhibitory activity and the latent activable collagenase in tissue samples obtained from patients with IPF and HP

MATERIALS AND METHODS

contemplation Population

We studied five patients with IPF, four women and united man, aged 31 to 57 years of long date mean age: 42.4 years; and six female patients with chronic HP with age ranging from 23 to 45 years elderly with a mean of 313 years. All patients of the one and the other groups fulfilled the clinical criteria for diagnosis described elsewhere.[5,13-15] The diagnosis was confirmed by means of the morphologic findings in the tissue samples obtained end an open lung biopsy. Briefly, lung tissue from IPF patients showed diffuse alveolar septal fibrosis, and interstitial and intra-alveolar inflammation, consisting for the most part of mononuclear cells but also of neutrophils and eosinophils. There was no evidence of granuloma or vasculitis and no inorganic material was construct by polarized light microscopy. There was in all samples a predominance of fibrotic lesions through inflammatory ones. Tissue samples of HP patients showed a diffuse interstitial inflammation of mononuclear predominance, mainly lymphocyte and many times multinucleated giant cells were seen in terminal and respiratory bronchioles as well as in the interalveolar walls. Foamy macrophages were observ in the alveolar spaces, and small and loosely arranged granulomas were near in interstitium. The lung tissue showed a clear predominance of inflammatory alterations with a slight standing of fibrosis. Finally, in all cases, biopsy agricultures were negative for bacteria, mycobacteria and fungi, and no changes suggestive of another interstitial lung disease were institute In addition, HP patients instanted a history of close outlook to avian antigens and all of them had positive serum-specific precipitating antibodies to pigeon antigens determined according to an enzyme-linked immunosorbent assay (ELISA). The average duration of symptoms at the time of lung biopsy was 154 [+ or -] 41 month for IPF patients, and 112 [+ or -] 36 month for HP patients. None of them in either assemblage was a cigarette smoker, and all patients had, at the time of the inquiry reticulonodular images spread over the pair lungs on chest roentgenogram.