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Normal neutrophil functions in sphingosine kinase type 1 and 2 knockout mice.

Zemann, Barbara, Urtz, Nicole, Reuschel, Roland, Mechtcheriakova, Diana, Bornancin, Frederic, Badegruber, Rudolf, Baumruker, Thomas and Billich, Andreas (2007) Normal neutrophil functions in sphingosine kinase type 1 and 2 knockout mice. Immunology Letters, 109 (1). pp. 56-63. ISSN 0165-2478


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.

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Additional Information: author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Keywords: Sphingosine kinase; Neutrophils; Knockout mice
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Date Deposited: 14 Dec 2009 13:58
Last Modified: 31 Jan 2013 01:14