Rho GTPase Rac1 is critical for neutrophil migration into the lung.
Neutrophils are critical in the inflammatory process by moving rapidly to tissue sites of inflammation. Members of the small Rho GTPase family, Rac1, Rac2, CDC42, and RhoA, are central regulators of cell migration by cytoskeleton rearrangement. The role of Rac1 in neutrophil migration related to inflammatory processes has remained elusive and has yet to be determined in physiologic in vivo models. We previously demonstrated a role for Rac1 in tail retraction. Here, we present evidence that Rac1-mediated uropod formation may be due to crosstalk with a related Rho GTPase RhoA. To assess the physiologic relevance of these findings, we used adoptive transfer of Rac1flox/flox bone marrow cells which allows postengraftment in vivo deletion of Rac1 only in blood cells. We examined the specific role of Rac1 in neutrophil migration into the lung during the inflammatory process induced by formyl-methionyl-leucyl-phenylalanine exposure. The loss of Rac1 activity in neutrophils is associated with a significant decreased neutrophil recruitment into lung alveolar and attenuation of emphysematous lesions. Overall, this study suggests that Rac1 is a physiologic integrator of signals for neutrophil recruitment into lung tissue during an inflammatory response.
Filippi
Marie-Dominique
MD
Division Experimental Hematology, Cincinnati Children's Research Foundation, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, OH 45229, USA. Marie-Dominique.Filippi@cchmc.org
Szczur
Kathleen
K
Harris
Chad E
CE
Berclaz
Pierre-Yves
PY
D000818:Animals; D001773:Blood Cells; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation; D004646:Emphysema / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced; D008168:Lung / Q000473:pathology*; D051379:Mice; D020556:Neutrophil Infiltration; D015398:Signal Transduction; D014161:Transduction, Genetic; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000502:physiology*
C107953:RAC1 protein, human; D020830:rac1 GTP-Binding Protein