PMID- 20562701 OWN - NLM STAT- MEDLINE DCOM- 20100817 LR - 20100721 IS - 1530-0293 (Electronic) IS - 0090-3493 (Linking) VI - 38 IP - 8 DP - 2010 Aug TI - Bone marrow-derived mononuclear cell therapy in experimental pulmonary and extrapulmonary acute lung injury. PG - 1733-41 LID - 10.1097/CCM.0b013e3181e796d2 [doi] AB - OBJECTIVE: To hypothesize that bone marrow-derived mononuclear cell (BMDMC) therapy might act differently on lung and distal organs in models of pulmonary or extrapulmonary acute lung injury with similar mechanical compromises. The pathophysiology of acute lung injury differs according to the type of primary insult. DESIGN: Prospective, randomized, controlled, experimental study. SETTING: University research laboratory. MEASUREMENTS AND MAIN RESULTS: In control animals, sterile saline solution was intratracheally (0.05 mL) or intraperitoneally (0.5 mL) injected. Acute lung injury animals received Escherichia coli lipopolysaccharide intratracheally (40 microg, ALIp) or intraperitoneally (400 microg, ALIexp). Six hours after lipopolysaccharide administration, ALIp and ALIexp animals were further randomized into subgroups receiving saline (0.05 mL) or BMDMC (2 x 10) intravenously. On day 7, BMDMC led to the following: 1) increase in survival rate; 2) reduction in static lung elastance, alveolar collapse, and bronchoalveolar lavage fluid cellularity (higher in ALIexp than ALIp); 3) decrease in collagen fiber content, cell apoptosis in lung, kidney, and liver, levels of interleukin-6, KC (murine interleukin-8 homolog), and interleukin-10 in bronchoalveolar lavage fluid, and messenger RNA expression of insulin-like growth factor, platelet-derived growth factor, and transforming growth factor-beta in both groups, as well as repair of basement membrane, epithelium and endothelium, regardless of acute lung injury etiology; 4) increase in vascular endothelial growth factor levels in bronchoalveolar lavage fluid and messenger RNA expression in lung tissue in both acute lung injury groups; and 5) increase in number of green fluorescent protein-positive cells in lung, kidney, and liver in ALIexp. CONCLUSIONS: BMDMC therapy was effective at modulating the inflammatory and fibrogenic processes in both acute lung injury models; however, survival and lung mechanics and histology improved more in ALIexp. These changes may be attributed to paracrine effects balancing pro- and anti-inflammatory cytokines and growth factors, because a small degree of pulmonary BMDMC engraftment was observed. FAU - Araujo, Indianara M AU - Araujo IM AD - Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Abreu, Soraia C AU - Abreu SC FAU - Maron-Gutierrez, Tatiana AU - Maron-Gutierrez T FAU - Cruz, Fernanda AU - Cruz F FAU - Fujisaki, Livia AU - Fujisaki L FAU - Carreira, Humberto Jr AU - Carreira H Jr FAU - Ornellas, Felipe AU - Ornellas F FAU - Ornellas, Debora AU - Ornellas D FAU - Vieira-de-Abreu, Adriana AU - Vieira-de-Abreu A FAU - Castro-Faria-Neto, Hugo C AU - Castro-Faria-Neto HC FAU - Muxfeldt Ab'Saber, Alexandre AU - Muxfeldt Ab'Saber A FAU - Teodoro, Walcy R AU - Teodoro WR FAU - Diaz, Bruno L AU - Diaz BL FAU - Peres Dacosta, Carlos AU - Peres Dacosta C FAU - Capelozzi, Vera L AU - Capelozzi VL FAU - Pelosi, Paolo AU - Pelosi P FAU - Morales, Marcelo M AU - Morales MM FAU - Rocco, Patricia R M AU - Rocco PR LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Crit Care Med JT - Critical care medicine JID - 0355501 RN - 0 (Cytokines) RN - 0 (Lipopolysaccharides) RN - 0 (Platelet-Derived Growth Factor) RN - 0 (RNA, Messenger) RN - 0 (Transforming Growth Factor beta) RN - EC 3.4.22.- (Caspase 3) SB - IM MH - Acute Lung Injury/chemically induced/mortality/physiopathology/*therapy MH - Animals MH - Apoptosis/*physiology MH - Bone Marrow Transplantation/*methods MH - Bronchoalveolar Lavage Fluid/cytology MH - Caspase 3/metabolism MH - Cytokines/*metabolism MH - Disease Models, Animal MH - Escherichia coli MH - Female MH - Leukocytes, Mononuclear/transplantation MH - Lipopolysaccharides MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Microscopy, Confocal MH - Microscopy, Electron MH - Platelet-Derived Growth Factor/metabolism MH - RNA, Messenger/metabolism MH - Random Allocation MH - Reference Values MH - Respiratory Mechanics/*physiology MH - Reverse Transcriptase Polymerase Chain Reaction MH - Survival Rate MH - Transforming Growth Factor beta/metabolism EDAT- 2010/06/22 06:00 MHDA- 2010/08/18 06:00 CRDT- 2010/06/22 06:00 PHST- 2010/06/22 06:00 [entrez] PHST- 2010/06/22 06:00 [pubmed] PHST- 2010/08/18 06:00 [medline] AID - 10.1097/CCM.0b013e3181e796d2 [doi] PST - ppublish SO - Crit Care Med. 2010 Aug;38(8):1733-41. doi: 10.1097/CCM.0b013e3181e796d2.