Syntaxin-11 is expressed in primary human monocytes/macrophages and acts as a negative regulator of macrophage engulfment of apoptotic cells and IgG-opsonized target cells.
Syntaxin-11 is a member of a family of membrane-trafficking proteins referred to as soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). Recent studies have shown that syntaxin-11 is expressed in natural killer cells and cytotoxic T cells and is likely to play a role in the granule exocytosis pathway. However, the biological role of syntaxin-11 in other immune cells has remained elusive. This study found that stimulation with interferon-gamma upregulated syntaxin-11 expression in primary monocytes. Experiments using monocytes from patients with familial haemophagocytic lymphohistiocytosis harbouring mutations in the gene encoding syntaxin-11 (STX11), or monocytes from healthy individuals in which syntaxin-11 was downregulated using specific short-interfering RNA, demonstrated that syntaxin-11 was not required for antibody-dependent cellular cytotoxicity. On the other hand, silencing of syntaxin-11 expression in primary macrophages enhanced the phagocytosis of apoptotic target cells with a concomitant increase in macrophage secretion of tumour necrosis factor-alpha. Moreover, Fcgamma-receptor-mediated uptake of target cells was also enhanced following silencing of syntaxin-11 expression in macrophages. In addition, syntaxin-11 localized to the plasma membrane in macrophages ingesting apoptotic cell corpses. Syntaxin-11 thus appears to act as a negative regulator of human macrophage engulfment of apoptotic cells and IgG-opsonized red blood cells.
Zhang
Shouting
S
Division of Biochemical Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Ma
Daoxin
D
Wang
Xiangling
X
Celkan
Tiraje
T
Nordenskjöld
Magnus
M
Henter
Jan-Inge
JI
Fadeel
Bengt
B
Zheng
Chengyun
C
D016022:Case-Control Studies; D002478:Cells, Cultured; D004912:Erythrocytes / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D051359:Lymphohistiocytosis, Hemophagocytic / Q000276:immunology* / Q000378:metabolism; D009000:Monocytes / Q000502:physiology*; D052066:N-Ethylmaleimide-Sensitive Proteins / Q000378:metabolism; D010587:Phagocytosis / Q000502:physiology*; D050765:Qa-SNARE Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins / Q000378:metabolism; D018709:Statistics, Nonparametric
D007074:Immunoglobulin G; D050765:Qa-SNARE Proteins; D034741:RNA, Small Interfering; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D007371:Interferon-gamma; D052066:N-Ethylmaleimide-Sensitive Proteins