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Production of TNF‐α by polymorphonuclear leukocytes during mechanical ventilation in the surfactant‐depleted rabbit lung
Author(s) -
Noda Eri,
Hoshina Hiroaki,
Watanabe Hiroshi,
Kawano Toshio
Publication year - 2003
Publication title -
pediatric pulmonology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.866
H-Index - 106
eISSN - 1099-0496
pISSN - 8755-6863
DOI - 10.1002/ppul.10370
Subject(s) - medicine , tumor necrosis factor alpha , lung , mechanical ventilation , pulmonary surfactant , ventilation (architecture) , alveolar macrophage , macrophage , pathology , immunology , andrology , biology , in vitro , biochemistry , mechanical engineering , engineering
Previous studies showed that the production of tumor necrosis factor‐α (TNF‐α) and the number of recovered cells were much higher in the conventional mechanical ventilation (CMV) group than in the high‐frequency oscillation (HFO) group at the end of mechanical ventilation in this model. But the type of cells that generated TNF‐α in the lungs remained unclear. It was shown that the alveolar macrophage was the source of TNF‐α in the early stage, but that in the later stage, the cells in the lung lavage fluid contained almost no macrophages. Thus we hypothesized that in the surfactant‐depleted lung model, one of the sources of TNF‐α after 4 hr of CMV is polymorphonuclear leukocyte (PMN), a type of cell which was numerous at that time. We performed the experiment in the same lung lavage model. The results were as follows. All Pa0 2 values for the HFO group were significantly greater than the corresponding values for the CMV group throughout the experiment ( P < 0.05). More than 96% of the recovered cells of the lung lavage fluid at the end of ventilation were PMN. Cell counts after ventilation of HFO and CMV groups were 183.0 ± 40.8 (mean ± SD, n = 6)/μl and 1,106.0 ± 310.0/μl, respectively ( P < 0.05). Levels of rabbit TNF‐α in the lavage fluid before and after 4 hr ventilation were 43.3 ± 103.7 pg/ml and 2,406.0 ± 1,525.1 pg/ml, respectively, in the CMV group. In the HFO group, these levels were 26.6 ± 52.0 pg/ml and 613.3 ± 362.2 pg/ml, respectively. The level of TNF‐α was significantly greater in the CMV group after ventilation ( P < 0.05). We performed RT‐PCR analysis, in which we showed the presence of TNF‐α mRNA in the intraalveolar cells (PMN) after 4 hr of CMV, and then demonstrated a positive immunofluorescence reaction to anti‐TNF‐α antibody in PMN separated from the lavage fluid. Our conclusion is that in this surfactant‐depleted lung model, PMN is one of the sources of TNF‐α in the lavage fluid after 4 hr of CMV. Pediatr Pulmonol. 2003; 36:475–481. © 2003 Wiley‐Liss, Inc.