Keratinocyte growth factor pretreatment is associated with decreased macrophage inflammatory protein-2alpha concentrations and reduced neutrophil recruitment in acid aspiration lung injury.
A two-hit model of acid aspiration was used to examine the effect of keratinocyte growth factor (KGF) on chemokine levels and neutrophil recruitment into the lung. Mice were subjected to cecal ligation and puncture and then either KGF or saline, intratracheally (i.t.). Forty-eight hours later, the mice were given i.t. acid. After 8 h, neutrophil counts in bronchoalveolar lavage (BAL) fluid were significantly decreased in animals pretreated with KGF (23 +/- 4 x 10(3)/mouse) compared with saline (74 +/- 2 x 10(3)/mouse). In addition, the BAL fluid IL-6 levels were decreased in the KGF-treated group (88+/- 44 pg/mL) compared with the saline group (166 +/- 34 pg/mL). To examine the mechanism behind the KGF-induced reduction in neutrophil influx, the murine chemokines KC and macrophage inflammatory protein (MIP)-2alpha were measured. KC levels in plasma and BAL fluid were not significantly different between the treatment groups. Likewise, levels of MIP-2alpha in plasma were not affected by KGF treatment. However, 8 h after acid aspiration, MIP-2alpha concentrations were significantly lower in the KGF-treated group. The ratio of MIP-2alpha in BAL fluid versus plasma was lower in the KGF group (0.72 +/- 0.28) than in the saline group at 3 h (2.23 +/- 0.93) and also significantly lower in the KGF group (3.02 +/- 0.78) compared with the saline group (6.23 +/- 1.19) at 8 h. In this study, KGF pretreatment after acid aspiration was associated with reduced neutrophil recruitment into the lung and a decrease in MIP-2alpha gradients between BAL fluid and plasma.
Nemzek
Jean A
JA
Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109-0602, USA.
Ebong
Samuel J
SJ
Kim
Jiyoun
J
Bolgos
Gerald L
GL
Remick
Daniel G
DG
D000818:Animals; D001772:Blood Cell Count; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D054426:Chemokine CXCL2; D018925:Chemokines / Q000032:analysis / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000008:administration & dosage* / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D015846:Monokines / Q000378:metabolism*; D020556:Neutrophil Infiltration / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D011015:Pneumonia, Aspiration / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology
D054426:Chemokine CXCL2; D018925:Chemokines; C496454:Fgf7 protein, mouse; D015846:Monokines; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors