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Activation of a Plasma Membrane-Associated Neutral
Sphingomyelinase and Concomitant Ceramide Accumulation During
IgG-Dependent Phagocytosis in Human Polymorphonuclear Leukocytes
Vania Hinkovska-Galcheva,
Lars Kjeldsen,
Pamela J. Mansfield,
Laurence A. Boxer,
James A. Shayman, and
Suzanne J. Suchard
From the Department of Pediatrics, the Division of
Hematology/Oncology and the Department of Internal Medicine, the
Division of Nephrology, University of Michigan, Ann Arbor, MI.
The sphingomyelin cycle, which plays an important role in regulation
of cell growth, differentiation, and apoptosis, involves the formation
of ceramide by the action of a membrane-associated, Mg2+-dependent, neutral sphingomyelinase and/or a
lysosomal acid sphingomyelinase. In human polymorphonuclear leukocytes
(PMNs), ceramide production correlates with and plays a role in the
regulation of functional responses such as oxidant release and Fc
receptor-mediated phagocytosis. To increase our understanding of the
sphingomyelin cycle in human PMNs, the cellular location of neutral and
acid sphingomyelinases was investigated in resting,
formylmethionylleucylphenylalanine (FMLP)-activated, and FMLP-activated
PMNs engaged in phagocytosis. In resting PMNs, a
Mg2+-dependent, neutral sphingomyelinase was the
predominant activity and was localized to the plasma membrane fractions
along with the majority of ceramide. Upon FMLP-activation, there was a
1.9-fold increase in this neutral, Mg2+-dependent
sphingomyelinase activity, which increased to 2.7-fold subsequent to
phagocytosis of IgG opsonized targets. This increase in
sphingomyelinase activity was restricted to the plasma membrane fractions, which were also the site of increased ceramide levels. Phospholipase D (PLD) activity, which is a target of ceramide action
and is required for phagocytosis, was also found primarily in the
plasma membrane fractions of FMLP-activated and phagocytosing PMNs. Our
findings indicate that in human PMNs engaged in phagocytosis, the
sphingomyelin cycle is restricted to the plasma membrane where intracellular targets of ceramide action, such as PLD, are localized.
Blood, Vol. 91 No. 12 (June 15), 1998:
pp. 4761-4769
© 1998 by The American Society of Hematology.
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