Impact of sex and ozone exposure on the course of pneumonia in wild type and SP-A (−/−) mice

Abstract

Female mice exhibited higher survival rate than males after pneumonia, with a reversal of this pattern following ozone exposure. Surfactant protein A (SP-A) plays an important role in innate immunity and SP-A (−/−) mice were more susceptible to pneumonia than wild type mice. Here, we investigated underlying mechanisms of the differential susceptibility of mice to pneumonia. Wild type and SP-A (−/−) C57BL/6J male and female mice were exposed to ozone or filtered air (FA) and then infected intratracheally with Klebsiella pneumoniae. Blood, spleen, and lung were analyzed for bacterial counts, lung and spleen weights, and sex hormone and cortisol levels were measured in plasma within two days post-infection. We found: 1) in the absence of ozone-induced oxidative stress, males had higher level of bacterial dissemination compared to females; ozone exposure decreased pulmonary clearance in both sexes and ozone-exposed females were more affected than males; 2) ozone exposure increased lung weight, but decreased spleen weight in both sexes, and in both cases ozone-exposed females were affected the most; 3) plasma cortisol levels in infected mice changed: ozone-exposed > FA-exposed, females > males, and infected > non-infected; 4) no major sex hormone differences were observed in the studied conditions; 5) differences between wild type and SP-A (−/−) mice were observed in some of the studied conditions. We concluded that reduced pulmonary clearance, compromised spleen response to infection, and increased cortisol levels in ozone-exposed females, and the higher level of lung bacterial dissemination in FA-exposed males, contribute to the previously observed survival outcomes.

Effect of ozone exposure and infection on bronchoalveolar lavage: Sex differences in response patterns

“…Our previous work [22] where bacterial load was assessed at 24 and 48 hr after the instillation of bacteria and after FA or ozone exposure, indicates that the increased %PMN after ozone exposure may be a consequence of increased bacterial CFU (or decreased clearance).…”

“…We have shown that male and female mice differ in their abilities to combat infection, and that oxidative stress, in the form of acute ozone exposure, affects this response [18,21,22,26,27]. Our goal in the current study was to study BAL factors that may contribute to these differences.…”

“…In a series of publications we have described sex differences [18,21,22,26,27] in outcome after infecting mice with Klebsiella pneumoniae , with or without a prior oxidative stress in the form of an acute ozone exposure. The above studies include differences in survival and phagogcytosis of pathogens by alveolar macrophages [18,21,25] as well as differences in histopathology and dissemination of the resulting infection [22,27].…”

“…The above studies include differences in survival and phagogcytosis of pathogens by alveolar macrophages [18,21,25] as well as differences in histopathology and dissemination of the resulting infection [22,27]. Moreover, we have shown that the sex differences persist and are accentuated in mice lacking SP-A or after the oxidative modification of SP-A [18,21].…”

Usefulness of gender and abnormal blood count for predicting pneumonia outcome in children

“…Sex differences in the local innate defence of the lung as a phagocytic effect of alveolar macrophage and the effect of sex hormones on phagocytic cells of the lung may explain these results. These differences were evidenced in mice where males were more susceptible to pneumonia than females however after acquiring infection, in the presence of ozone exposure females were more affected than males [28]. Further studies in this topic in humans are recommended to better explain the disparity of alveolar macrophage function among both sexes.…”