Article
Bone marrow-derived mononuclear cell therapy in experimental pulmonary and extrapulmonary acute lung injury
Registro en:
ARAÚJO, Indianara M. et al. Bone marrow-derived mononuclear cell therapy in experimental pulmonary and extrapulmonary acute lung injury. Crit Care Med., v.38, n.8, p.1733-1741, 2010.
0090-3493
10.1097/CCM.0b013e3181e796d2
1530-0293
Autor
Abreu, Adriana Vieira de
Faria Neto, Hugo C. Castro
Múltipla autoria - ver em Notas
Resumen
AUTHORS AND AFFILIATIONS: From the Laboratory of Pulmonary Investigation (IMA,
SCA, TM-G, FC, LF, HC, DO, PRMR), Carlos Chagas Filho
Institute of Biophysics, Federal University of Rio de Janeiro,
Rio de Janeiro, Brazil; Laboratory of Immunopharmacology
(AV-d-A, HCC-F-N), Oswaldo Cruz Institute,
FIOCRUZ, Rio de Janeiro, Brazil; Laboratory of Cellular
and Molecular Physiology (TM-G, FO, DO, MMM), Carlos
Chagas Filho Institute of Biophysics, Federal University
of Rio de Janeiro, Rio de Janeiro, Brazil; Department of
Pathology (MA, VLC), School of Medicine, University of
Sa˜o Paulo, Sa˜o Paulo, Brazil; Department of Rheumatology
(WRT), University of Sa˜o Paulo, Sa˜o Paulo, Brazil;
Laboratory of Inflammation (BLD), Carlos Chagas Filho
Institute of Biophysics, Federal University of Rio de Janeiro,
Rio de Janeiro, Brazil; Department of Physiology
and Pharmacology (CPD), Federal University of Pernambuco,
Recife, Pernambuco, Brazil; and the Department of
Ambient, Health and Safety (PP), University of Insubria,
Varese, Italy. 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 g, ALIp) or intraperitoneally
(400 g, ALIexp). Six hours after lipopolysaccharide
administration, ALIp and ALIexp animals were further randomized
into subgroups receiving saline (0.05 mL) or BMDMC (2 106)
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- 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. 2030-01-01