Normal neutrophil functions in sphingosine kinase type 1 and 2 knockout mice.
Sphingosine kinase (SPHK) has been implicated as an important element in neutrophil responses to diverse stimulatory agents. To get more insight into the role of the type 1 and 2 isoforms of SPHK in neutrophil functions, we made use of the respective SPHK knockout mice. Neutrophils isolated from the bone marrow of these mice showed normal increase of intracellular Ca(2+) when stimulated in vitro by fMLP, platelet-activating factor, the anaphylatoxin C5a, or ATP, and normal migration towards fMLP and C5a. Also, recruitment of neutrophils into the peritoneum towards the chemokines KC and MIP-2 or to LPS, and into the peripheral blood after fMLP injection was similar in SPHK knockout strains and wild-type animals. An in vivo model of bacterial lung infection revealed an accelerated progression of disease in SPHK2 (but not SPHK1) knockout mice as compared to wild-type controls. However, effector functions of SPHK-deficient neutrophils, such as superoxide production, beta-glucuronidase release and their capacity to kill bacteria were unchanged as compared to wild-type cells. To conclude, the data derived from SPHK knockout mice do not support the hypothesis that any of the two lipid kinases plays a crucial role in signalling downstream of various neutrophil stimuli; SPHKs appear not to be essential for neutrophil recruitment and effector functions.
Zemann
Barbara
B
Novartis Institutes for BioMedical Research, Vienna, Brunnerstrasse 59, A-1235 Wien, Austria.
Urtz
Nicole
N
Reuschel
Roland
R
Mechtcheriakova
Diana
D
Bornancin
Frédéric
F
Badegruber
Rudolf
R
Baumruker
Thomas
T
Billich
Andreas
A
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000172:deficiency* / Q000276:immunology / Q000378:metabolism; D011008:Pneumococcal Infections / Q000201:enzymology / Q000276:immunology; D013296:Streptococcus pneumoniae; D000099157:Sphingosine Kinase
D002118:Calcium; D017853:Phosphotransferases (Alcohol Group Acceptor); D000099157:Sphingosine Kinase