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Originally published online as doi:10.1189/jlb.1007672 on March 13, 2008

Published online before print March 13, 2008
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(Journal of Leukocyte Biology. 2008;83:1493-1501.)
© 2008 by Society for Leukocyte Biology

An age-associated increase in pulmonary inflammation after burn injury is abrogated by CXCR2 inhibition

Vanessa Nomellini*,{dagger},{ddagger}, Douglas E. Faunce{dagger},{ddagger},§, Christian R. Gomez{dagger},{ddagger},§ and Elizabeth J. Kovacs{dagger},{ddagger},§,||,1

* Program in Cellular and Molecular Biochemistry,
{dagger} Burn and Shock Trauma Institute, Departments of
§ Surgery and
|| Cell Biology, Neurobiology and Anatomy, and
{ddagger} Immunology and Aging Program, Loyola University Medical Center, Maywood, Illinois, USA

1Correspondence: Loyola University Medical Center, Department of Surgery, Bldg. 110, Room 4232, 2160 South First Avenue, Maywood, IL 60153, USA. E-mail: ekovacs{at}lumc.edu

ABSTRACT

Burn patients over the age of 60 are at a greater risk for developing pulmonary complications than younger patients. The mechanisms for this, however, have yet to be elucidated. The objective of this study was to determine whether increased chemoattraction plays a role in the age-related differences in pulmonary inflammation after burn injury. At 6 or 24 h after receiving sham or 15% total body surface area scald injury, lungs from young and aged mice were analyzed for leukocyte content by histological examination and immunostaining. Lungs were then homogenized, and levels of neutrophil chemokines, MIP-2 and KC, were measured. At 6 h after burn, the number of neutrophils was four times higher in the lungs of both burn groups compared with aged-matched controls (P<0.05), but no age difference was evident. At 24 h, in contrast, neutrophils returned to sham levels in the lungs of young, burn-injured mice (P<0.05) but did not change in the lungs of aged, burn-injured mice. Pulmonary levels of the neutrophil chemokine KC but not MIP-2 were consistently three times higher in aged, burn-injured mice compared with young, burn-injured mice at both time-points analyzed. Administration with anti-CXCR2 antibody completely abrogated the excessive pulmonary neutrophil content by 24 h (P<0.05), while not affecting the inflammatory response of the wounds. These studies show that CXCR2-mediated chemoattraction is involved in the pulmonary inflammatory response after burn and suggest that aged individuals sustaining a burn injury may benefit from treatment strategies that target neutrophil chemokines.

Key Words: aging • acute lung injury • KC • macrophage inflammatory protein-2 • neutrophil






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