IJPPP Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Physiol Pathophysiol Pharmacol 2011;3(3):176-190.

Original Article
Histopathologic evaluation of lung and extrapulmonary tissues show sex
differences in Klebsiella pneumoniae - infected mice under different exposure

Anatoly N. Mikerov, Timothy K. Cooper, Guirong Wang, Sanmei Hu, Todd M. Umstead, David S. Phelps, Joanna Floros

Center for Host defense, Inflammation, and Lung Disease (CHILD) Research, Department of Pediatrics; Department of Comparative
Medicine; Department of Pathology; and Department of Obstetrics and Gynecology, The Pennsylvania State University College of
Medicine, Hershey, PA 17033, USA.

Received July 21, 2011; accepted August 10, 2011; Epub September 6, 2011; Published September 30, 2011

Abstract: It has been shown that female mice with pneumonia have a survival advantage over males, but this is reversed if ozone
exposure precedes infection. The purpose of this study was to investigate factors that underlie these observations, by studying
histopathologic changes in lung and extrapulmonary (spleen and liver) tissues after ozone or filtered air (FA) exposure followed by
pulmonary bacterial infection. Male and female wild type C57BL/6J mice were exposed to ozone or FA, then anesthetized and infected
intratracheally with Klebsiella pneumoniae bacteria. Tissues (lung, spleen, and liver) were subjected to histopathologic analysis at 48
h post-infection. We found that after infection, 1) the severity of inflammation was higher, the affected area of the lung was larger, and
spleen red pulp myelopoiesis was lower in ozone-exposed mice compared to FA-exposed animals in both sexes; 2) more pronounced
extrapulmonary lesions (in liver and spleen) were observed in FA-exposed males compared to FA-exposed females; and 3) excessive
lung inflammatory response was detected in ozone-exposed females compared to ozone-exposed males. We concluded that different
risk factors contribute to the differential outcome of pneumonia between sexes in the presence or absence of ozone-induced oxidative
stress. In specific, the excessive lung inflammation and higher risk for extrapulmonary lesions in ozone-exposed infected females and
in FA-exposed infected males appear to play, respectively, a dominant role in the previously observed respective survival outcomes.   

Keywords: Sex, infection, lung inflammation, spleen function, pathology

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Address all correspondence to:
Joanna Floros, PhD
Center for Host defense, Inflammation, and Lung Disease (CHILD) Research
Department of Pediatrics, H085, The Pennsylvania State University College of Medicine
500 University Drive, Hershey, PA 17033, USA.
Tel: (717) 531-6972; Fax: (717) 531-0215; E-mail: jfloros@psu.edu