title: Endothelial cell changes are associated with pulmonary edema and respiratory distress in mice infected with the WA1 human Babesia parasite.
abstract: A C3H/HeN mouse model was established to study the pathogenesis of the human babesial parasites, WA1 and Babesia microti. To evaluate the course of parasitemia and the associated lesions, mice were inoculated intraperitoneally with either WA1-infected, B. microti-infected, or uninfected hamster red blood cells. WA1-infected mice developed dyspnea and moderate parasitemias, after which death occurred. Babesia microti-infected mice experienced low parasitemias with no apparent morbidity or mortality. WA1-infected mice were thrombocytopenic but not anemic. Hemograms for B. microti-infected mice were similar to controls. Postmortem examination of WA1-infected mice revealed prominent lesions in the lungs, including pulmonary edema and intravascular margination of leukocytes. No pulmonary changes were detected in B. microti-infected mice. Blood gas measurements of WA1-infected mice showed reduced oxygen saturation and pH, and increased carbonic acid compared to controls, indicating hypoxia and respiratory acidosis. Ultrastructure studies of WA1-infected lungs showed hypertrophied endothelial cells containing transcellular channels associated with protein-rich intra-alveolar fluid. Endothelial cell activation was demonstrated by an upregulation of intercellular adhesion molecule-1 in the lungs of WA1-infected mice. The results suggest that recruitment of inflammatory cells to the lungs in WA1-infected mice induces endothelial cell alterations, leading to pulmonary edema and acute respiratory failure.
authors.affiliation: Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis 95616, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Hemmer
authors.forename: E J
authors.initials: EJ
authors.lastname: Wozniak
authors.forename: L J
authors.initials: LJ
authors.lastname: Lowenstine
authors.forename: C G
authors.initials: CG
authors.lastname: Plopper
authors.forename: V
authors.initials: V
authors.lastname: Wong
authors.forename: P A
authors.initials: PA
authors.lastname: Conrad
mesh_terms: D000818:Animals; D001404:Babesiosis / Q000097:blood / Q000473:pathology* / Q000503:physiopathology; D001784:Blood Gas Analysis; D004195:Disease Models, Animal; D004906:Erythrocyte Count; D005260:Female; D006400:Hematocrit; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D007958:Leukocyte Count; D008168:Lung / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D008809:Mice, Inbred C3H; D018512:Parasitemia / Q000097:blood / Q000473:pathology* / Q000503:physiopathology; D010976:Platelet Count; D011507:Proteinuria / Q000652:urine; D011654:Pulmonary Edema / Q000097:blood / Q000473:pathology* / Q000503:physiopathology; D011897:Random Allocation; D012131:Respiratory Insufficiency / Q000097:blood / Q000473:pathology* / Q000503:physiopathology; D013047:Specific Pathogen-Free Organisms; D013997:Time Factors
chemical_list: D018799:Intercellular Adhesion Molecule-1