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

我们最近报道了Hermansky-Pudlak综合征(HPS)相关性间质性肺炎(HPSIP)肺部II型肺泡泡状肿胀/变性(巨板层体变性；GLBD)的持续存在，提出了GLBD可能是HPSIP发生发展的触发因素的假说(Virchow Arch，2000)。我们现在研究了白耳(EP)小鼠(HPS1的小鼠模型)和米色(BG)小鼠(Chediak-Higashi综合征(CHS)的小鼠模型)的肺病理，特别是GLBD和相关的病理变化。GLBD在EP和BG小鼠出生后不久就被发现，随着小鼠年龄的增长，GLBD的严重程度增加。年轻的小鼠只表现出GLBD，没有间质改变的证据。老年BG小鼠(22~24月龄)以GLBD最为突出，8只小鼠中有3只伴有淋巴细胞浸润，肺泡间隔塌陷轻度纤维化，肺泡内巨噬细胞浸润。老年EP小鼠(24月龄)的GLBD程度低于年龄相当的BG小鼠，也有轻微的间质炎症倾向，但没有纤维化。这些小鼠肺泡上皮细胞表面活性蛋白B免疫反应阳性，超微结构上由板层结构组成，与人肺小球上皮细胞几乎相同。本研究结果支持GLBD可能在HPSIP的发生发展中起重要作用的假说。EP和BG小鼠，特别是后者，可能是一种有用的HPSIP小鼠模型。

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.