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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Leukoc+Biol
2016 ; 100
(1
): 131-41
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PLA2G5 regulates transglutaminase activity of human IL-4-activated M2 macrophages
through PGE2 generation
#MMPMID26936936
Yamaguchi M
; Zacharia J
; Laidlaw TM
; Balestrieri B
J Leukoc Biol
2016[Jul]; 100
(1
): 131-41
PMID26936936
show ga
Phospholipases A2 are enzymes that liberate membrane-bound lipids in a tissue and
cell-specific fashion. Group V secretory phospholipase A2 is necessary for the
development of M2 macrophages and their effector functions in a mouse model of
the T-helper-2 allergic airway inflammation. However, the function of group V
phospholipase A2 in human M2 activation and T-helper-2 inflammation is
ill-defined. Transglutaminase-2, a protein cross-linking enzyme, is a newly
identified marker of both human and mouse interleukin-4-activated M2 macrophages
and is also found in the lungs of patients with asthma. We report that group V
phospholipase A2 and transglutaminase-2 colocalized in macrophages of human nasal
polyp tissue obtained from patients with T-helper-2 eosinophilic inflammation,
and their coexpression positively correlated with the number of eosinophils in
each tissue specimen. We demonstrate that in human monocyte-derived macrophages
activated by interleukin-4, group V phospholipase A2 translocated and colocalized
with transglutaminase-2 in the cytoplasm and on the membrane of macrophages.
Moreover, knocking down group V phospholipase A2 with small interfering
ribonucleic acid reduced macrophage transglutaminase activity, whereas mass
spectrometry analysis of lipids also showed reduced prostaglandin E2 production.
Finally, exogenous prostaglandin E2 restored transglutaminase activity of group V
phospholipase A2-small interfering ribonucleic acid-treated macrophages. Thus,
our study shows a novel function of group V phospholipase A2 in regulating the
transglutaminase activity of human interleukin-4-activated M2 macrophages through
prostaglandin E2 generation and suggests that group V phospholipase A2 is a
functionally relevant enzyme that may have therapeutic value for the treatment of
human T-helper-2 inflammatory disorders.