TY - JOUR
T1 - Role of macrophage inflammatory protein-2 in aspiration-induced lung injury
AU - Shanley, Thomas P.
AU - Vasi, Neeti
AU - Davidson, Bruce A.
AU - Nader, Nader D.
AU - Knight, Paul R.
AU - Bless, Nicholas
AU - Ward, Peter A.
AU - Johnson, Kent J.
PY - 2000
Y1 - 2000
N2 - Objective: To determine the role of the chemokine, macrophage inflammatory protein (MIP)-2, in the pathogenesis of aspiration-induced lung injury in the rat. Design: Prospective, randomized, controlled animal study. Setting: University research laboratories. Subjects: Adult, male Long-Evans rats. Interventions: Anesthetized rats underwent induction of lung injury by well-described models of aspiration triggered by intratracheal delivery of acid alone, gastric particles alone, or the combination. After injury, induction of MIP-2 messenger RNA in whole lungs and immunoreactive MIP-2 in bronchoalveolar lavage (BAL) fluids was determined. The contribution of MIP-2 to BAL fluid chemotactic activity was defined by using an in vitro chemotaxis assay. The in vitro effect of blocking MIP-2 on pulmonary vascular leak, BAL fluid neutrophils, PaO2/FIO2 ratio, and alveolar-arterial oxygen tension gradient in acid-induced lung injury was determined. Measurements and Main Results: Induction of MIP-2 messenger RNA and protein over time was observed in response to all three stimuli. A significant portion (25% to 41%) of the chemotactic activity in BAL fluids from injured rats was inhibited by anti- MIP-2 antibody. After acid injury, blocking of MIP-2 was associated with a 53% decrease in BAL fluid neutrophils and a 33% decrease in pulmonary vascular leak. Although acid injury both impaired oxygenation and increased venous admixture, in vivo blocking of MIP-2 was associated with improved oxygenation as well as decreased venous admixture. Conclusions: MIP-2 was up- regulated during the development of aspiration-induced lung injury in rats. MIP-2 contributed to lung accumulation of neutrophils via a chemotactic mechanism. Although oxygenation and venous admixture are worsened by acid- induced lung injury in vivo, blocking of MIP-2 at the onset of injury improved these physiologic alterations. Because the aspiration event often is witnessed, chemokines may be valid therapeutic targets for inhibiting the subsequent inflammatory response.
AB - Objective: To determine the role of the chemokine, macrophage inflammatory protein (MIP)-2, in the pathogenesis of aspiration-induced lung injury in the rat. Design: Prospective, randomized, controlled animal study. Setting: University research laboratories. Subjects: Adult, male Long-Evans rats. Interventions: Anesthetized rats underwent induction of lung injury by well-described models of aspiration triggered by intratracheal delivery of acid alone, gastric particles alone, or the combination. After injury, induction of MIP-2 messenger RNA in whole lungs and immunoreactive MIP-2 in bronchoalveolar lavage (BAL) fluids was determined. The contribution of MIP-2 to BAL fluid chemotactic activity was defined by using an in vitro chemotaxis assay. The in vitro effect of blocking MIP-2 on pulmonary vascular leak, BAL fluid neutrophils, PaO2/FIO2 ratio, and alveolar-arterial oxygen tension gradient in acid-induced lung injury was determined. Measurements and Main Results: Induction of MIP-2 messenger RNA and protein over time was observed in response to all three stimuli. A significant portion (25% to 41%) of the chemotactic activity in BAL fluids from injured rats was inhibited by anti- MIP-2 antibody. After acid injury, blocking of MIP-2 was associated with a 53% decrease in BAL fluid neutrophils and a 33% decrease in pulmonary vascular leak. Although acid injury both impaired oxygenation and increased venous admixture, in vivo blocking of MIP-2 was associated with improved oxygenation as well as decreased venous admixture. Conclusions: MIP-2 was up- regulated during the development of aspiration-induced lung injury in rats. MIP-2 contributed to lung accumulation of neutrophils via a chemotactic mechanism. Although oxygenation and venous admixture are worsened by acid- induced lung injury in vivo, blocking of MIP-2 at the onset of injury improved these physiologic alterations. Because the aspiration event often is witnessed, chemokines may be valid therapeutic targets for inhibiting the subsequent inflammatory response.
KW - Acid aspiration
KW - Chemokines
KW - Lung injury
KW - Macrophage inflammatory protein-2
KW - Neutrophils
KW - Particulate aspiration
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U2 - 10.1097/00003246-200007000-00041
DO - 10.1097/00003246-200007000-00041
M3 - Article
C2 - 10921576
AN - SCOPUS:0033852631
SN - 0090-3493
VL - 28
SP - 2437
EP - 2444
JO - Critical Care Medicine
JF - Critical Care Medicine
IS - 7
ER -