Pulmonary vascular remodeling correlates with lung eggs and cytokines in murine schistosomiasis.
BACKGROUND
Schistosomiasis is considered to be the most common worldwide cause of pulmonary hypertension. At present there is no well-characterized animal model to study the pathobiology of this important condition.


OBJECTIVE
To develop a mouse model of schistosomiasis, characterize the extent of pulmonary vascular remodeling, and determine the potential role of inflammatory cytokines.


METHODS
Mice (C57/Bl6) were infected transcutaneously with a high dose (approximately 75-100 cercariae) or a low dose (approximately 30 cercariae) of Schistosoma mansoni, and the development of lung and liver pathology was studied in the subacute (high-dose) and chronic (low-dose) settings.


RESULTS
In the subacute setting, mice showed few eggs in the lungs and no evidence of pulmonary vascular remodeling. In contrast, chronically infected animals had a much greater lung egg burden and developed marked pulmonary vascular remodeling accompanied by perivascular inflammation from 12 weeks onwards. In addition, we observed the presence of plexiform-like lesions in these mice. Lung egg burden correlated with both liver egg burden and right ventricular (RV) index in the chronic group, although significant RV hypertrophy was lacking. Plasma Th1 and Th2 cytokines increased with time in the chronic group and correlated with the degree of pulmonary vascular remodeling.


CONCLUSIONS
This study provides evidence for extensive pulmonary vascular remodeling, despite the absence of RV hypertrophy, in a mouse model of schistosomiasis, including the formation of plexiform-like lesions. Inflammatory cytokines and lung egg burden may contribute to vascular lesion formation.
Crosby
Alexi
A
Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom.
Jones
Frances M
FM
Southwood
Mark
M
Stewart
Susan
S
Schermuly
Ralph
R
Butrous
Ghazwan
G
Dunne
David W
DW
Morrell
Nicholas W
NW
D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D008168:Lung / Q000469:parasitology* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010784:Photomicrography; D011651:Pulmonary Artery / Q000473:pathology*; D012550:Schistosoma mansoni / Q000302:isolation & purification*; D012552:Schistosomiasis / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D014655:Vascular Resistance / Q000502:physiology*
D016207:Cytokines