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

Zemann, Barbara and Urtz, Nicole and Reuschel, Roland and Mechtcheriakova, Diana and Bornancin, Frederic and Badegruber, Rudolf and 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.

Item Type: Article
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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


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