Activated mast cells release extracellular type platelet-activating factor acetylhydrolase that contributes to autocrine inactivation of platelet-activating factor.
IgE-dependent and -independent activation of mouse bone marrow-derived mast cells (BMMC) elicited rapid and transient production of platelet-activating factor (PAF), which reached a maximal level by 2-5 min and was then degraded rapidly, returning to base-line levels by 10-20 min. Inactivation of PAF was preceded by the release of PAF acetylhydrolase (PAF-AH) activity, which reached a plateau by 3-5 min and paralleled the release of beta-hexosaminidase, a marker of mast cell exocytosis. Immunochemical and molecular biological studies revealed that the PAF-AH released from activated mast cells was identical to the plasma-type isoform. In support of the autocrine action of exocytosed PAF-AH, adding exogenous recombinant plasma-type PAF-AH markedly reduced PAF accumulation in activated BMMC. Furthermore, culture of BMMC with a combination of c-kit ligand, interleukin-1beta and interleukin-10 for > 24 h led to an increase in plasma-type PAF-AH expression, accompanied by a reduction in stimulus-initiated PAF production. Collectively, these results suggest that plasma-type PAF-AH released from activated mast cells sequesters proinflammatory PAF produced by these cells, thereby revealing an intriguing anti-inflammatory aspect of mast cells.
Nakajima
K
K
Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Japan.
Murakami
M
M
Yanoshita
R
R
Samejima
Y
Y
Karasawa
K
K
Setaka
M
M
Nojima
S
S
Kudo
I
I
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D001854:Bone Marrow Cells; D000001:Calcimycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008407:Mast Cells / Q000201:enzymology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010741:Phospholipases A / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000378:metabolism; D019089:Stem Cell Factor / Q000378:metabolism; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D007476:Ionophores; D010972:Platelet Activating Factor; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D000001:Calcimycin; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D001619:beta-N-Acetylhexosaminidases