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 acetylhydrola se (PAF-AH) activity, which reached a plateau by 3-5 min and parallele d the release of beta-hexosaminidase, a marker of mast cell exocytosis . Immunochemical and molecular biological studies revealed that the PA F-AH released from activated mast cells was identical to the plasma-ty pe isoform. In support of the autocrine action of exocytosed PAF-AH, a dding exogenous recombinant plasma-type PAF-AH markedly reduced PAF ac cumulation in activated BMMC. Furthermore, culture of BMMC with a comb ination of c-kit ligand, interleukin-1 beta and interleukin-10 for > 2 4 h led to an increase in plasma-type PAF-AH expression, accompanied b y a reduction in stimulus-initiated PAF production. Collectively, thes e 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.