Parasite burden and CD36-mediated sequestration are determinants of acute lung injury in an experimental malaria model.
Parasite burden and CD36-mediated sequestration are determinants of acute lung injury in an experimental malaria model.
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DOI：
10.1371/journal.ppat.1000068
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发表时间：
2008-05-16
期刊：
影响因子：
6.7
通讯作者：
Kain KC
中科院分区：
文献类型：
--
作者：
Lovegrove FE;Gharib SA;Peña-Castillo L;Patel SN;Ruzinski JT;Hughes TR;Liles WC;Kain KC
Although acute lung injury (ALI) is a common complication of severe malaria, little is known about the underlying molecular basis of lung dysfunction. Animal models have provided powerful insights into the pathogenesis of severe malaria syndromes such as cerebral malaria (CM); however, no model of malaria-induced lung injury has been definitively established. This study used bronchoalveolar lavage (BAL), histopathology and gene expression analysis to examine the development of ALI in mice infected with Plasmodium berghei ANKA (PbA). BAL fluid of PbA-infected C57BL/6 mice revealed a significant increase in IgM and total protein prior to the development of CM, indicating disruption of the alveolar–capillary membrane barrier—the physiological hallmark of ALI. In contrast to sepsis-induced ALI, BAL fluid cell counts remained constant with no infiltration of neutrophils. Histopathology showed septal inflammation without cellular transmigration into the alveolar spaces. Microarray analysis of lung tissue from PbA-infected mice identified a significant up-regulation of expressed genes associated with the gene ontology categories of defense and immune response. Severity of malaria-induced ALI varied in a panel of inbred mouse strains, and development of ALI correlated with peripheral parasite burden but not CM susceptibility. Cd36 −/− mice, which have decreased parasite lung sequestration, were relatively protected from ALI. In summary, parasite burden and CD36-mediated sequestration in the lung are primary determinants of ALI in experimental murine malaria. Furthermore, differential susceptibility of mouse strains to malaria-induced ALI and CM suggests that distinct genetic determinants may regulate susceptibility to these two important causes of malaria-associated morbidity and mortality. Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) can occur in adult malaria infections with a case fatality rate of 70%–100%. ALI and ARDS are characterized by protein-rich fluid in the lungs, with reduced gas exchange, and in malaria, often accompany high parasite levels and severe or cerebral disease. In this work we have examined lung physiology, pathology and genomics in mouse malaria—Plasmodium berghei ANKA—to show that mice develop malaria-induced ALI. Infected mice have proteinaceous fluid in their lungs, have a migration of inflammatory cells from the blood into the lung walls, and express immune response–related genes. We also found that severity of ALI depended on high parasite levels, both overall and specifically in the lung tissue, but was not consistent with whether the mice developed cerebral malaria. ALI due to Plasmodium berghei ANKA infection models prominent characteristics of human malaria-associated ALI, and we have better defined this model of malaria ALI so it may be used to further explore disease mechanisms and eventual treatment.
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DOI：
10.1086/510756
发表时间：
2007-02-15
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Anstey NM;Handojo T;Pain MC;Kenangalem E;Tjitra E;Price RN;Maguire GP
通讯作者：
Maguire GP
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
7
作者：
Ashburner, M;Ball, CA;Yoon, J
通讯作者：
Yoon, J
DOI：
10.1046/j.1440-1843.2001.00324.x
发表时间：
2001-06-01
期刊：
Respirology (Carlton, Vic.)
影响因子：
--
作者：
Gupta, D;Ramanathan, R P;Jindal, S K
通讯作者：
Jindal, S K
影响因子：
64.8
作者：
Aitman, TJ;Cooper, LD;Scott, J
通讯作者：
Scott, J