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Molecular and Cellular Biology, February 2003, p. 1034-1043, Vol. 23, No. 3
0270-7306/03/$08.00+0 DOI: 10.1128/MCB.23.3.1034-1043.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
Loss of S100A9 (MRP14) Results in Reduced Interleukin-8-Induced CD11b Surface Expression, a Polarized Microfilament System, and Diminished Responsiveness to Chemoattractants In Vitro
Marie-Pierre Manitz,1 Basil Horst,1 Stephan Seeliger,1 Anke Strey,2 Boris V. Skryabin,3 Matthias Gunzer,4 Werner Frings,1 Frank Schönlau,1 Johannes Roth,1 Clemens Sorg,1 and Wolfgang Nacken1*
Institute of Experimental Dermatology,1
Institute of Medical Biochemistry,2
Institute of Experimental Pathology, Zentrum für Molekularbiologie der Entzündung,3
Department of Dermatology, Ludwig Boltzmann Institute of Cell Biology, University of Münster, 48149 Münster, Germany4
Received 15 August 2002/
Returned for modification 13 September 2002/
Accepted 22 October 2002
The S100A9 (MRP14) protein is abundantly expressed in myeloid cells and has been associated with various inflammatory diseases. The S100A9-deficient mice described here were viable, fertile, and generally of healthy appearance. The myelopoietic potential of the S100A9-null bone marrow was normal. S100A8, the heterodimerization partner of S100A9 was not detectable in peripheral blood cells, suggesting that even a deficiency in both S100A8 and S100A9 proteins was compatible with viable and mature neutrophils. Surprisingly, the invasion of S100A9-deficient leukocytes into the peritoneum and into the skin in vivo was indistinguishable from that in wild-type mice. However, stimulation of S100A9-deficient neutrophils with interleukin-8 in vitro failed to provoke an up-regulation of CD11b. Migration upon a chemotactic stimulus through an endothelial monolayer was markedly diminished in S100A9-deficient neutrophils. Attenuated chemokinesis of the S100A9-deficient neutrophils was observed by using a three-dimensional collagen matrix migration assay. The altered migratory behavior was associated with a microfilament system that was highly polarized in unstimulated S100A9-deficient neutrophils. Our data suggest that loss of the calcium-binding S100A9 protein reduces the responsiveness of the neutrophils upon chemoattractant stimuli at least in vitro. Alternative pathways for neutrophil emigration may be responsible for the lack of any effect in the two in vivo models we have investigated so far.
* Corresponding author. Mailing address: Institute of Experimental Dermatology, Von Esmarch Str. 58, 48149 Münster, Germany. Phone: 49-251-8356552. Fax: 49-251-8356549. E-mail: nacken{at}uni-muenster.de.
Molecular and Cellular Biology, February 2003, p. 1034-1043, Vol. 23, No. 3
0022-538X/03/$08.00+0 DOI: 10.1128/MCB.23.3.1034-1043.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
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Copyright © 2003 by the American Society for Microbiology. All rights reserved.