| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Published online before print December 19, 2005
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
* Infectious Diseases Division and Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston;
Department of Physics, Massachusetts Institutes of Technology, Boston;
Cardiovascular Medicine Unit, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, Hammersmith Hospital, United Kingdom;
Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Shriners Hospitals for Children, and Harvard Medical School, Boston; and
¶ Endocrine Unit, Massachusetts General Hospital, Boston
1 Correspondence: Infectious Diseases Division, Massachusetts General Hospital (East), 149 13th Street, Room 5212, Charlestown Navy Yard, Boston, MA 02129. E-mail: mpoznansky{at}partners.org
We report for the first time that primary human neutrophils can undergo persistent, directionally biased movement away from a chemokine in vitro and in vivo, termed chemorepulsion or fugetaxis. Robust neutrophil chemorepulsion in microfluidic gradients of interleukin-8 (IL-8; CXC chemokine ligand 8) was dependent on the absolute concentration of chemokine, CXC chemokine receptor 2 (CXCR2), and was associated with polarization of cytoskeletal elements and signaling molecules involved in chemotaxis and leading edge formation. Like chemoattraction, chemorepulsion was pertussis toxin-sensitive and dependent on phosphoinositide-3 kinase, RhoGTPases, and associated proteins. Perturbation of neutrophil intracytoplasmic cyclic adenosine monophosphate concentrations and the activity of protein kinase C isoforms modulated directional bias and persistence of motility and could convert a chemorepellent to a chemoattractant response. Neutrophil chemorepulsion to an IL-8 ortholog was also demonstrated and quantified in a rat model of inflammation. The finding that neutrophils undergo chemorepulsion in response to continuous chemokine gradients expands the paradigm by which neutrophil migration is understood and may reveal a novel approach to our understanding of the homeostatic regulation of inflammation.
Key Words: chemotaxis • microfluidics • gradient
This article has been cited by other articles:
|
|
 |
|
  T. R. Wuest and D. J. J. Carr Dysregulation of CXCR3 Signaling due to CXCL10 Deficiency Impairs the Antiviral Response to Herpes Simplex Virus 1 Infection J. Immunol., December 1, 2008; 181(11): 7985 - 7993. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Prakash, M. H. de Borst, M. Lacombe, F. Opdam, P. A. Klok, H. van Goor, D. K.F. Meijer, F. Moolenaar, K. Poelstra, and R. J. Kok Inhibition of Renal Rho Kinase Attenuates Ischemia/Reperfusion-Induced Injury J. Am. Soc. Nephrol., November 1, 2008; 19(11): 2086 - 2097. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Dumont, K. Lepage, C. H. Cote, and J. Frenette Mast cells can modulate leukocyte accumulation and skeletal muscle function following hindlimb unloading J Appl Physiol, July 1, 2007; 103(1): 97 - 104. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Mathias, B. J. Perrin, T.-X. Liu, J. Kanki, A. T. Look, and A. Huttenlocher Resolution of inflammation by retrograde chemotaxis of neutrophils in transgenic zebrafish J. Leukoc. Biol., December 1, 2006; 80(6): 1281 - 1288. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
