Title: Regulation of inflammation by Rac2 in immune complex-mediated acute lung injury
Authors: Dooley, James ×
Abdel-Latif, Dalia
St Laurent, Chris D
Puttagunta, Lakshmi
Befus, Dean
Lacy, Paige #
Issue Date: Dec-2009
Publisher: Amer physiological soc
Series Title: American Journal of Physiology. Lung Cellular and Molecular Physiology vol:297 issue:6 pages:L1091-L1102
Abstract: Dooley JL, Abdel-Latif D, St. Laurent CD, Puttagunta L, Befus D, Lacy P. Regulation of inflammation by Rac2 in immune complex-mediated acute lung injury. Am J Physiol Lung Cell Mol Physiol 297: L1091-L1102, 2009. First published October 2, 2009; doi:10.1152/ajplung.90471.2008.-Acute lung injury (ALI) is an inflammatory disorder associated with recruitment and activation of neutrophils in lungs. Rac2, a member of the Rho GTPase subfamily, is an essential regulator of neutrophil degranulation, superoxide release, and chemotaxis. Here, we hypothesized that Rac2 is important in mediating lung injury. Using a model of IgG immune complex-mediated ALI, we showed that injury was attenuated in rac2(-/-) mice compared with wild-type (WT) mice undergoing ALI, with significant decreases in alveolar leukocyte numbers, vascular leakage, and the inflammatory mediators, myeloperoxidase (MPO) and matrix metalloproteinases ( MMPs). Reduced injury in rac2(-/-) mice was not associated with diminished cytokine and chemokine production, since bronchoalveolar lavage (BAL) levels of IL-17, TNF, CCL3, CXCL1, and CXCL2 were similarly increased in WT and rac2(-/-) mice with ALI compared with sham-treated mice (no ALI). BAL levels of MMP-2 and MMP-9 were significantly decreased in the airways of rac2(-/-) mice with ALI. Immunohistochemical analysis revealed that MMP-2 and MMP-9 expression was evident in alveolar macrophages and interstitial neutrophils in WT ALI. In contrast, MMP-positive cells were less prominent in rac2(-/-) mice with ALI. Chimeric mice showed that Rac2-mediated lung injury was dependent on hematopoietic cells derived from bone marrow. We propose that lung injury in response to immune complex deposition is dependent on Rac2 in alveolar macrophages and neutrophils.
ISSN: 1040-0605
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Genetics of Autoimmunity
× corresponding author
# (joint) last author

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