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Ceramide inhibits IgG-dependent phagocytosis in human polymorphonuclear
leukocytes
SJ Suchard, V Hinkovska-Galcheva, PJ Mansfield, LA Boxer and JA Shayman
Department of Pediatrics, University of Michigan, Ann Arbor 48109, USA.
Ceramide is a product of agonist-induced sphingolipid metabolism in several
cell types, including polymorphonuclear leukocytes (PMNs). In adherent
PMNs, the kinetics of ceramide production correspond with the termination
of fMLP-stimulated H2O2 release. Furthermore, short chain ceramides inhibit
fMLP-mediated H2O2 release in adherent PMNs. In the present study, we
investigated the effects of short chain ceramides and sphingoid bases on
phagocytosis of IgG-opsonized erythrocytes (EIgG) by suspended PMNs
activated with fMLP. N-Acetylsphingosine, N- acetylphytosphingosine,
phytosphingosine, sphingosine, and dihydrosphingosine, but not
N-acetyldihydrosphingosine, inhibited phagocytosis of EIgG. In contrast,
these same lipids did not inhibit fMLP-mediated chemotaxis. Endogenous
ceramide levels increased within the first few minutes of phagocytosis,
with a significant (P < .05) accumulation by 30 minutes, the time by
which phagocytosis was terminated. Neutral sphingomyelinase activity
paralleled the increase in ceramide, consistent with the generation of
ceramide by the hydrolysis of sphingomyelin. The N-acetyl-conjugated
sphingols (C2 ceramides) blocked phosphatidylethanol formation indicating
that phospholipase D (PLD) is an intracellular target of ceramide action.
These data suggest that ceramides, generated through activation of the
sphingomyelin cycle, act as negative regulators of Fc(gamma)R-mediated
phagocytosis.
Volume 89,
Issue 6,
pp. 2139-2147,
03/15/1997
Copyright © 1997 by The American Society of Hematology
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