Role of neutrophils in lung vascular injury and edema after premature birth in lambs.

To investigate the role of neutrophils in the pathogenesis of respiratory distress after premature birth, we assessed the relationship between circulating neutrophil concentration and neutrophil accumulation in the lung, lung lymph and pleural liquid flow, and extravascular lung water in 10 chronically catheterized preterm lambs (127 +/- 1 days gestation) that were mechanically ventilated for 8 h after birth. Circulating neutrophil concentration transiently decreased within 2 h after birth and then returned to prenatal values by 6-8 h. The decrease in circulating neutrophil concentration was related directly to the accumulation of neutrophils in the air spaces, drainage of liquid and protein from the lung 6-8 h after delivery, and postmortem extravascular lung water. In additional studies, we intravenously administered mechlorethamine to 5 fetal lambs to reduce circulating neutrophils before delivery (neutrophil concentration before birth: 9 +/- 11 cells/microl). Compared with control lambs, neutrophil-depleted lambs had significantly less drainage of liquid (7.8 +/- 5.9 vs. 2.6 +/- 1.9 ml/h, respectively) and protein (116 +/- 74 vs. 42 +/- 27 mg/h, respectively) from the lung 6-8 h after birth and significantly less extravascular lung water at postmortem (6.5 +/- 0. 8 vs. 4.8 0.6 g/g dry lung, respectively). Thus neutrophils contribute to the pathogenesis of respiratory distress after premature birth by increasing lung vascular protein permeability and promoting lung edema.

[1]  M. Baggiolini.  Activation and recruitment of neutrophil leukocytes , 1995, Clinical and experimental immunology.

[2]  D. Carlton,et al.  Surfactant Treatment at Birth Reduces Lung Vascular Injury and Edema in Preterm Lambs , 1995, Pediatric Research.

[3]  R. Demling.  The modern version of adult respiratory distress syndrome. , 1995, Annual review of medicine.

[4]  L. Povirk,et al.  DNA damage and mutagenesis induced by nitrogen mustards. , 1994, Mutation research.

[5]  D. Carlton,et al.  Lung vascular protein permeability in preterm fetal and mature newborn sheep. , 1994, Journal of applied physiology.

[6]  K. Miyasaka,et al.  Role of high-frequency ventilation in surfactant-depleted lung injury as measured by granulocytes. , 1994, Journal of applied physiology.

[7]  G. Downey,et al.  Neutrophils increase volume during migration in vivo and in vitro. , 1994, American journal of respiratory cell and molecular biology.

[8]  S. Peters,et al.  Physical and cytochemical properties of neutrophils activated in situ in the lung during ZAP infusion in sheep. , 1993, Journal of applied physiology.

[9]  K. Albertine,et al.  CELL INTERACTIONS IN THE LUNG , 1993 .

[10]  R. Barton,et al.  Interactions of leukocyte integrins with intercellular adhesion molecule 1 in the production of inflammatory vascular injury in vivo. The Shwartzman reaction revisited. , 1992, The Journal of clinical investigation.

[11]  R. Rothlein,et al.  Monoclonal Antibodies to the Leukocyte Membrane CD18 Glycoprotein Complex and to Intercellular Adhesion Molecule‐1 Inhibit Leukocyte‐Endothelial Adhesion in Rabbits , 1991, Journal of leukocyte biology.

[12]  J. Wiener-Kronish,et al.  Clearance of lung edema into the pleural space of volume-loaded anesthetized sheep. , 1990, Journal of applied physiology.

[13]  T. Carlos,et al.  Membrane Proteins Involved in Phagocyte Adherence to Endothelium , 1990, Immunological reviews.

[14]  D. Carlton,et al.  Lung fluid balance in lambs before and after premature birth. , 1989, The Journal of clinical investigation.

[15]  K. Albertine.  Lung injury and neutrophil density during air embolization in sheep after leukocyte depletion with nitrogen mustard. , 1988, The American review of respiratory disease.

[16]  M. Matthay,et al.  Relationship of pleural effusions to increased permeability pulmonary edema in anesthetized sheep. , 1988, The Journal of clinical investigation.

[17]  E. Chi,et al.  Sequence of inflammatory cell migration into lung during recovery from hyaline membrane disease in premature newborn monkeys. , 1987, The American review of respiratory disease.

[18]  M. Cybulsky,et al.  Effect of granulocyte depletion in a ventilated surfactant-depleted lung. , 1987, Journal of applied physiology.

[19]  P. Dorinsky,et al.  Lung neutrophils in the adult respiratory distress syndrome. Clinical and pathophysiologic significance. , 1986, The American review of respiratory disease.

[20]  A. Jobe,et al.  Lung protein leaks in ventilated lambs: effects of gestational age. , 1985, Journal of applied physiology.

[21]  John D. Johnson,et al.  Neonatal lung neutrophils and elastase/proteinase inhibitor imbalance. , 2015, The American review of respiratory disease.

[22]  J. Hogg,et al.  TRANSIENT LEUCOPENIA ASSOCIATED WITH ADULT RESPIRATORY DISTRESS SYNDROME , 1984, The Lancet.

[23]  C. Plopper,et al.  Triamcinolone-induced structural alterations in the development of the lung of the fetal rhesus macaque. , 1984, American journal of obstetrics and gynecology.

[24]  D. Strayer,et al.  Elastase and alpha 1-proteinase inhibitor activity in tracheal aspirates during respiratory distress syndrome. Role of inflammation in the pathogenesis of bronchopulmonary dysplasia. , 1983, The Journal of clinical investigation.

[25]  A. Malik,et al.  Granulocytes mediate the increase in pulmonary vascular permeability after thrombin embolism. , 1983, Journal of applied physiology: respiratory, environmental and exercise physiology.

[26]  G. Zimmerman,et al.  Functional and metabolic activity of granulocytes from patients with adult respiratory distress syndrome. Evidence for activated neutrophils in the pulmonary circulation. , 1983, The American review of respiratory disease.

[27]  T. Hazinski,et al.  Lung fluid balance in lambs before and after birth. , 1982, Journal of applied physiology: respiratory, environmental and exercise physiology.

[28]  T. Allen Merritt.  Oxygen Exposure in the Newborn Guinea Pig Lung Lavage Cell Populations, Chemotactic and Elastase Response: a Possible Relationship to Neonatal Bronchopulmonary Dysplasia , 1982 .

[29]  K. Brigham,et al.  Prevention by granulocyte depletion of increased vascular permeability of sheep lung following endotoxemia. , 1981, The Journal of clinical investigation.

[30]  A. Perel,et al.  Leukocytes Are Required for Increased Lung Microvascular Permeability after Microembolization in Sheep , 1981, Circulation research.

[31]  P. Ballard,et al.  Radioimmunoassay of pulmonary surface-active material in the tracheal fluid of the fetal lamb. , 2015, The American review of respiratory disease.

[32]  R. Bland,et al.  Lung fluid dynamics in awake newborn lambs. , 1977, The Journal of clinical investigation.

[33]  J. Kitterman,et al.  Surfactant in the lung and tracheal fluid of the fetal lamb and acceleration of its appearance by dexamethasone. , 1975, Pediatrics.

[34]  K. Brigham,et al.  Effect of Increased Vascular Pressure on Lung Fluid Balance in Unanesthetized Sheep , 1975, Circulation research.

[35]  E. Motoyama,et al.  Morphologic development of fetal rabbit lung and its acceleration with cortisol. , 1971, The American journal of pathology.

[36]  E. Reynolds,et al.  Pulmonary lymph flow and the uptake of liquid from the lungs of the lamb at the start of breathing , 1967, The Journal of physiology.

[37]  J. Beazell,et al.  Measurement of Pulmonary Edema , 1965, Circulation research.

[38]  B. Ames,et al.  The role of polyamines in the neutralization of bacteriophage deoxyribonucleic acid. , 1960, The Journal of biological chemistry.

[39]  W. J. Dyer,et al.  A rapid method of total lipid extraction and purification. , 1959, Canadian journal of biochemistry and physiology.