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(American Journal of Pathology. 2004;164:1115-1127.)
© 2004 American Society for Investigative Pathology

Animal Model

Alveolar Septal Deposition of Immunoglobulin and Complement Parallels Pulmonary Hemorrhage in a Guinea Pig Model of Severe Pulmonary Leptospirosis

Jarlath E. Nally^*, Chavit Chantranuwat, Xiao-Yang Wu^*, Michael C. Fishbein, Martha M. Pereira^¶, João José Pereira da Silva^||, David R. Blanco^* and Michael A. Lovett^*

From the Division of Infectious Diseases, ^*Department of Medicine, University of California Los Angeles, Los Angeles, California; the Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; the Department of Microbiology, Immunology and Molecular Genetics; the Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California; and the National Reference Center for Leptospirosis, ^¶Instituto Oswaldo Cruz, Rio de Janeiro, Brazil; and the Department of Clinical Medicine, ^||Faculty of Medicine, Fluminense Federal University, Rio de Janeiro, Brazil

Human patients suffering from leptospirosis present with a diverse array of clinical manifestations, including the more severe and often fatal pulmonary form of the disease. The etiology of pulmonary hemorrhage is unclear. Isolates of Leptospira acquired from patients suffering from pulmonary hemorrhage were used to develop a guinea pig model of pulmonary hemorrhage. Gross findings post-infection confirmed extensive hemorrhage in the lungs and on peritoneal surfaces as the likely cause of death. Immunohistochemistry confirmed the presence of large numbers of leptospires in kidney, liver, intestinal tissues, and spleen, but few inflammatory cells were seen. In marked contrast, few leptospires were detected in infected hemorrhagic lung tissue. Blood chemistries and hematology did not reveal the etiology of the hemorrhage observed. There was no chemical or microscopic evidence for disseminated intravascular coagulation. To ascertain an immunopathologic role during disease, immunofluorescence was performed on infected lung tissues and confirmed the presence of IgM, IgG, IgA, and C3 along the alveolar basement membrane. This suggests that an autoimmune process may be the etiology of fatal pulmonary hemorrhage in leptospirosis.

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