Impact of bone marrow mononuclear cell administration route on lung and distal organs in pulmonary and extrapulmonary acute lung injury

The pathophysiology of acute lung injury (ALI) differs according to the type of insult. We hypothesized that the administration route of bone marrow-derived mononuclear cell (BMDMC) therapy might have different effects on lung and distal organs in models of pulmonary (p) or extrapulmonary (exp) ALI. Forty-eight C57BL/6 mice: 36 females and 12 males (20-25 g) were used. In control animals, sterile saline solution was intratracheally or intraperitoneally injected. whereas ALI animals received Escherichia coli lipopolysaccharide intratracheally (40 μg, ALIp) or intraperitoneally (400 μg, ALIexp). Six hours after lipopolysaccharide administration, ALIp and ALIexp animals were further randomized into subgroups receiving saline or BMDMC (2×10 6 ) intravenously (BMDMC iv ) or intratracheally (BMDMC it ). At day 7: 1) BMDMC iv and it decreased static elastance, alveolar collapse, collagen fiber content, and bronchoalveolar lavage fluid cellularity; 2) BMDMC it increased the number of green fluorescent protein (GFP)+ cells in lung in ALIp, while BMDMC iv increased GFP+ cells in kidney and liver in ALIexp; 3) BMDMC it induced greater reduction of lung apoptotic cells in ALIp, while BMDMC iv decreased lung, kidney and liver apoptosis in ALIexp; 4) BMDMC iv resulted in greater reduction in interleukin (IL)-6, KC (murine IL-8 homolog), and IL-10 compared to BMDMC it ; 5) the beneficial effects of BMDMC were independent of engraftment. In conclusion, BMDMC therapy was effective in modulating the inflammatory and fibrogenic process in both models, but greater beneficial effects were achieved with BMDMC iv . Supported by: FAPERJ, PRONEX, CNPq, CAPES