Loss of S100A9 (MRP14) results in reduced interleukin-8-induced CD11b surface expression, a polarized microfilament system, and diminished responsiveness to chemoattractants in vitro.
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.
Manitz
Marie-Pierre
MP
Institute of Experimental Dermatology, Zentrum für Molekularbiologie der Entzündung, Univeristy of Münster, 48149 Münster, Germany.
Horst
Basil
B
Seeliger
Stephan
S
Strey
Anke
A
Skryabin
Boris V
BV
Gunzer
Matthias
M
Frings
Werner
W
Schönlau
Frank
F
Roth
Johannes
J
Sorg
Clemens
C
Nacken
Wolfgang
W
D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism*; D040501:Calgranulin A / Q000378:metabolism; D040502:Calgranulin B / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D018390:Gene Targeting; D016209:Interleukin-8 / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D039481:CD11b Antigen; D040501:Calgranulin A; D040502:Calgranulin B; D016209:Interleukin-8; D003094:Collagen