The ex vivo perfused human lung is resistant to injury by high-dose S. pneumoniae bacteremia

Am J Physiol Lung Cell Mol Physiol. 2020 Aug 1;319(2):L218-L227. doi: 10.1152/ajplung.00053.2020. Epub 2020 Jun 10.


Few patients with bacteremia from a nonpulmonary source develop acute respiratory distress syndrome (ARDS). However, the mechanisms that protect the lung from injury in bacteremia have not been identified. We simulated bacteremia by adding Streptococcus pneumoniae to the perfusate of the ex vivo perfused human lung model. In contrast to a pneumonia model in which bacteria were instilled into the distal air spaces of one lobe, injection of high doses of S. pneumoniae into the perfusate was not associated with alveolar epithelial injury as demonstrated by low protein permeability of the alveolar epithelium, intact alveolar fluid clearance, and the absence of alveolar edema. Unexpectedly, the ex vivo human lung rapidly cleared large quantities of S. pneumoniae even though the perfusate had very few intravascular phagocytes and lacked immunoglobulins or complement. The bacteria were cleared in part by the small number of neutrophils in the perfusate, alveolar macrophages in the airspaces, and probably by interstitial pathways. Together, these findings identify one mechanism by which the lung and the alveolar epithelium are protected from injury in bacteremia.

Keywords: ARDS; acute lung injury; epithelial injury; sepsis; shock.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / microbiology*
  • Acute Lung Injury / pathology*
  • Adult
  • Bacteremia / microbiology
  • Bacteremia / pathology*
  • Epithelium / microbiology
  • Epithelium / pathology
  • Female
  • Humans
  • Lung / microbiology
  • Lung / pathology*
  • Macrophages / microbiology
  • Macrophages / pathology
  • Male
  • Middle Aged
  • Neutrophils / microbiology
  • Neutrophils / pathology
  • Permeability
  • Pneumococcal Infections / microbiology
  • Pneumococcal Infections / pathology
  • Pulmonary Alveoli / microbiology
  • Pulmonary Alveoli / pathology
  • Respiratory Distress Syndrome / microbiology
  • Respiratory Distress Syndrome / pathology
  • Respiratory Mucosa / microbiology
  • Respiratory Mucosa / parasitology
  • Streptococcus pneumoniae / pathogenicity*