OBJECTIVES: Neutrophils have been implicated in the pathogenesis of acute lung injury in bacteremic pneumococcal pneumonia. The characteristics of the population of neutrophils that injure the lung are still not known. This study was designed to compare the bone marrow release and lung sequestration of neutrophils during bacteremic pneumococcal pneumonia with nonbacteremic pneumonia and isolated bacteremia. DESIGN: Prospective, controlled, experimental study. SETTING: University research laboratory. SUBJECTS: Female New Zealand white rabbits (n = 17; weight 2.3 to 2.7 kg). INTERVENTIONS: The rabbits were pretreated with intravenous 5'-bromo-2-deoxyuridine (BrdU 100 mg/kg i.v.) to pulse label dividing neutrophils in the bone marrow. Twenty hours after the treatment with BrdU, the rabbits were anesthetized and pneumonia was induced by instilling Streptococcus pneumoniae (1.5 x 10(9) organisms) into the lower lobe of the lung. Four hours after pneumonia, bacteremia was induced by infusing S. pneumoniae (3.0 x 10(9) organisms) into the circulation (pneumonia + bacteremia: n = 6). These animals were compared with those with just pneumonia (n = 5) or bacteremia (n = 6). MEASUREMENTS AND MAIN RESULTS: White blood cell, neutrophil, and differential count. BrdU-labeled neutrophils (neutrophilBrdU) were identified using immunohistochemistry. Cells in tissues were examined microscopically, using sequential level stereologic analysis. The pneumonia + bacteremia group developed a leukopenia (7.3 +/- 0.7 to 2.4 +/- 0.2 x 10(9)/L) following the bacteremia that was associated with an increase in circulating band cells and neutrophilBrdU (2.3 +/- 0.8% to 33.5 +/- 2.8%) which were both higher than those in the other groups (p < .005). Bone marrow smears showed accelerated maturation of neutrophils in the pneumonia + bacteremia group (neutrophilBrdU increased from 11.6 +/- 1.0 to 45.3 +/- 2.1%). Morphometric studies of the lung showed increased neutrophil sequestration in the untreated lung tissue of the pneumonia + bacteremia group (16 +/- 0.8 x 10(8)/mL tissue) compared with the pneumonia (6.6 +/- 0.3 x 10(8)/mL tissue) and bacteremia (12 +/- 0.6 x 10(8)/mL tissue) groups (p < .0001). NeutrophilBrdU preferentially sequester in the lungs of all groups but were slow to migrate into the alveolar air spaces (p < .05). CONCLUSIONS: During bacteremic pneumococcal pneumonia there is an accelerated maturation of neutrophils in the bone marrow with an enhanced release of neutrophils into the circulation. These newly released neutrophils preferentially sequester in lung microvessels but are slow to migrate into the alveolar air space.
OBJECTIVES: Neutrophils have been implicated in the pathogenesis of acute lung injury in bacteremic pneumococcal pneumonia. The characteristics of the population of neutrophils that injure the lung are still not known. This study was designed to compare the bone marrow release and lung sequestration of neutrophils during bacteremic pneumococcal pneumonia with nonbacteremic pneumonia and isolated bacteremia. DESIGN: Prospective, controlled, experimental study. SETTING: University research laboratory. SUBJECTS: Female New Zealand white rabbits (n = 17; weight 2.3 to 2.7 kg). INTERVENTIONS: The rabbits were pretreated with intravenous 5'-bromo-2-deoxyuridine (BrdU 100 mg/kg i.v.) to pulse label dividing neutrophils in the bone marrow. Twenty hours after the treatment with BrdU, the rabbits were anesthetized and pneumonia was induced by instilling Streptococcus pneumoniae (1.5 x 10(9) organisms) into the lower lobe of the lung. Four hours after pneumonia, bacteremia was induced by infusing S. pneumoniae (3.0 x 10(9) organisms) into the circulation (pneumonia + bacteremia: n = 6). These animals were compared with those with just pneumonia (n = 5) or bacteremia (n = 6). MEASUREMENTS AND MAIN RESULTS: White blood cell, neutrophil, and differential count. BrdU-labeled neutrophils (neutrophilBrdU) were identified using immunohistochemistry. Cells in tissues were examined microscopically, using sequential level stereologic analysis. The pneumonia + bacteremia group developed a leukopenia (7.3 +/- 0.7 to 2.4 +/- 0.2 x 10(9)/L) following the bacteremia that was associated with an increase in circulating band cells and neutrophilBrdU (2.3 +/- 0.8% to 33.5 +/- 2.8%) which were both higher than those in the other groups (p < .005). Bone marrow smears showed accelerated maturation of neutrophils in the pneumonia + bacteremia group (neutrophilBrdU increased from 11.6 +/- 1.0 to 45.3 +/- 2.1%). Morphometric studies of the lung showed increased neutrophil sequestration in the untreated lung tissue of the pneumonia + bacteremia group (16 +/- 0.8 x 10(8)/mL tissue) compared with the pneumonia (6.6 +/- 0.3 x 10(8)/mL tissue) and bacteremia (12 +/- 0.6 x 10(8)/mL tissue) groups (p < .0001). NeutrophilBrdU preferentially sequester in the lungs of all groups but were slow to migrate into the alveolar air spaces (p < .05). CONCLUSIONS: During bacteremic pneumococcal pneumonia there is an accelerated maturation of neutrophils in the bone marrow with an enhanced release of neutrophils into the circulation. These newly released neutrophils preferentially sequester in lung microvessels but are slow to migrate into the alveolar air space.
Authors: Matthew J Delano; Kindra M Kelly-Scumpia; Terri C Thayer; Robert D Winfield; Philip O Scumpia; Alex G Cuenca; Phillips B Harrington; Kerri A O'Malley; Elizabeth Warner; Sonia Gabrilovich; Clayton E Mathews; Drake Laface; Paul G Heyworth; Reuben Ramphal; Robert M Strieter; Lyle L Moldawer; Philip A Efron Journal: J Immunol Date: 2011-06-20 Impact factor: 5.422
Authors: Bryan D Kraft; Claude A Piantadosi; Ashlee M Benjamin; Joseph E Lucas; Aimee K Zaas; Marisol Betancourt-Quiroz; Christopher W Woods; Alan L Chang; Victor L Roggli; Craig D Marshall; Geoffrey S Ginsburg; Karen Welty-Wolf Journal: Am J Respir Cell Mol Biol Date: 2014-05 Impact factor: 6.914