Acid sphingomyelinase is involved in CEACAM receptor-mediated phagocytosis of Neisseria gonorrhoeae.

Authors:
C R Hauck, H Grassmé, J Bock, V Jendrossek, K Ferlinz, T F Meyer, E Gulbins
Year of publication:
2000
Volume:
478
Issue:
3
Issn:
0014-5793
Journal title abbreviated:
FEBS Lett.
Journal title long:
FEBS letters
Impact factor:
3.864
Abstract:
The interaction with human phagocytes is a hallmark of symptomatic Neisseria gonorrhoeae infections. Gonococcal outer membrane proteins of the Opa family induce the opsonin-independent uptake of the bacteria that relies on CEACAM receptors and an active signaling machinery of the phagocyte. Here, we show that CEACAM receptor-mediated phagocytosis of Opa(52)-expressing N. gonorrhoeae into human cells results in a rapid activation of the acid sphingomyelinase. Inhibition of this enzyme by imipramine or SR33557 abolishes opsonin-independent internalization without affecting bacterial adherence. Reconstitution of ceramide, the product of acid sphingomyelinase activity, in imipramine- or SR33557-treated cells restores internalization of the bacteria. Furthermore, we demonstrate that CEACAM receptor-initiated stimulation of other signalling molecules, in particular Src-like tyrosine kinases and Jun N-terminal kinases, requires acid sphingomyelinase. These studies provide evidence for a crucial role of the acid sphingomyelinase for CEACAM receptor-initiated signalling events and internalization of Opa(52)-expressing N. gonorrhoeae into human neutrophils.