Sukura A, Konttinen Y T, Sepper R, Kaartinen L, Sorsa T, Lindberg L A
Department of Anatomy, College of Veterinary Medicine, University of Helsinki, Finland.
J Clin Microbiol. 1995 Apr;33(4):829-34. doi: 10.1128/jcm.33.4.829-834.1995.
Pneumocystis carinii pneumonia (PCP) is characterized by the formation of leaky alveoli and a foamy alveolar exudate. To induce PCP, male Wistar rats were immunosuppressed by oral dexamethasone treatment for 12 weeks, during which time all rats developed PCP. Bronchoalveolar lavage fluid (BALF) was analyzed at that time and at 1, 2, and 4 weeks after the cessation of dexamethasone treatment, during which time the rats were recovering from PCP and immunosuppression (and was compared with the BALF obtained from healthy control rats), for type IV collagenase, elastase, cathepsin G, and collagenase activities. Scores for 72-kDa (matrix metalloproteinase type [MMP-2]) and 92-kDa (MMP-9) type IV collagenase-gelatinase activities correlated with those for BALF macrophages (r = 0.58; P < 0.001) and neutrophils (r = 0.66; P < 0.001), respectively, suggesting that they may, in part, be derived from these cells. However, MMP-2 was constitutively expressed and may play a role in normal tissue remodeling. MMP-9 activity was highest in the group with PCP (1.8 +/- 0.37; P > 0.05), with a gradual decline (1.0 +/- 0.48 by week 4; P > 0.05) toward normal (0.67 +/- 0.42) during recovery, which suggests a role for it in tissue-destructive inflammatory events. In rats with PCP the endogenously active collagenase was present at high levels compared with those in healthy controls (2.6 +/- 0.69 versus 0.17 +/- 0.17, respectively; P < 0.01), but they returned to normal by week 4 of recovery (0.42 +/- 0.30; P > 0.05). Collagenase activity showed a correlation with cyst number (r = 0.57; P < 0.001). The BALF of rats with PCP also contained the serine proteinases, which may act as pro-MMP activators. Ultramorphology disclosed increased pinocytotic activities, subepithelial bleb formation, and degeneration and denudation of the basal lamina. These findings suggest that the increased activities of collagenases in BALF caused by the host response against P. carinii might contribute to leaky alveoli.
卡氏肺孢子虫肺炎（PCP）的特征是形成渗漏性肺泡和泡沫状肺泡渗出物。为诱发PCP，对雄性Wistar大鼠进行为期12周的口服地塞米松免疫抑制治疗，在此期间所有大鼠均患上PCP。在那时以及地塞米松治疗停止后的1、2和4周对支气管肺泡灌洗液（BALF）进行分析，在此期间大鼠从PCP和免疫抑制中恢复（并与从健康对照大鼠获得的BALF进行比较），检测IV型胶原酶、弹性蛋白酶、组织蛋白酶G和胶原酶活性。72 kDa（基质金属蛋白酶[MMP-2]型）和92 kDa（MMP-9）IV型胶原酶-明胶酶活性评分分别与BALF巨噬细胞评分（r = 0.58；P < 0.001）和中性粒细胞评分（r = 0.66；P < 0.001）相关，表明它们可能部分源自这些细胞。然而，MMP-2是组成性表达的，可能在正常组织重塑中起作用。MMP-9活性在PCP组中最高（1.8±0.37；P > 0.05），在恢复过程中逐渐下降（到第4周时为1.0±0.48；P > 0.05）至正常水平（0.67±0.42），这表明它在组织破坏性炎症事件中起作用。与健康对照相比，PCP大鼠内源性活性胶原酶水平较高（分别为2.6±0.69和0.17±0.17；P < 0.01），但在恢复的第4周时恢复正常（0.42±0.30；P > 0.05）。胶原酶活性与囊肿数量相关（r = 0.57；P < 0.001）。PCP大鼠的BALF中还含有丝氨酸蛋白酶，其可能作为MMP前体激活剂。超微形态学显示胞饮活性增加、上皮下气泡形成以及基膜变性和剥脱。这些发现表明，宿主对卡氏肺孢子虫的反应导致BALF中胶原酶活性增加可能导致肺泡渗漏。
