A study on pathogenesis of idiopathic interstitial pneumonia : Using ep mice, a mouse model of Hermansky-pudlak syndrome.

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We recently reported the constant presence of characteristic foamy swelling/degeneration (giant lamellar body degeneration ; GLBD) of type II pneumocytes in the lungs affected by Hermansky-Pudlak syndrome (HPS)-associated interstitial pneumonia (HPSIP), proposing the hypothesis that GLBD may be the triggering factor in the development of HPSIP (Virchows Arch, 2000). We now investigated the lung pathology of pale ear (ep) mouse, a mouse model of HPS1, and of beige (bg) mouse, a mouse model of Chediak-Higashi syndrome (CHS) with a special reference to GLBD and associated pathologic changes. GLBD was found both in ep and bg mice soon after birth, increasingin severity as mice grew older. Younger mice showed only GLBD with no evidence of interstitial change. Aged bg mice (22-24 months) showed the most prominent GLBD, 3 of the 8 cases showing associated lymphocytic infiltration and slight fibrosis of the collapsed alveolar septa as well as intraalveolar macrophage infiltration. Aged ep mice (24 months) with less severe GLBD than that of bg mice of comparative ages also showed a slight tendency to interstitial inflammation but no fibrosis. GLBs in these mice pneumocytes were immunoreactive for surfactant protein B and composed of lamellar structures ultrastructurally, almost identical to human GLBs. The results of the present study supports the hypothesis that GLBD may be playing an important role in the development of HPSIP. Ep and bg mice, especially the latter, may be a useful mouse model of HPSIP.