Platelet‐activating factor stimulates receptor‐mediated fromation of reactive oxygen intermediates in human monocytes

Породенко, Н. В.; Makarova, Olga; Kozyukov, A. V.; Moskaleva, E. Yu.; Sokolovsky, Alexander A.; Severin, E. S.

doi:10.1007/bf02536534

Cited by 6 publications

(1 citation statement)

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“…This is consistent with a previous study demonstrating that the treatment of human macrophages with higher concentration (10 −6 M) of PAF C-16 showed reduced phagocytosis of Leishmania braziliensis as compared to cells treated with the lower concentrations (10 −8 and 10 −10 M) (Borges et al, 2017). Similarly, human monocytes showed maximum production of ROIs when stimulated with PAF C-16 at 2 × 10 −6 M; increasing the concentration of PAF C-16 (5 × 10 −6 M) led to a decrease in ROIs production (Pustynnikov et al, 1991). The fact that PAF C-16 at higher concentrations (5 µg and 10 µg/ml) showed less intracellular growth inhibition than 1 µg/ml in our study, may be due to higher level of PAFR down regulation at these concentrations, as a result of the interaction of PAF C-16 with PAFR.…”

Section: Discussionmentioning

confidence: 88%

Dissecting the Mechanism of Intracellular Mycobacterium smegmatis Growth Inhibition by Platelet Activating Factor C-16

et al. 2020

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Mycobacterium tuberculosis (M.tb) infection results in approximately 1.3 million human deaths each year. M.tb resides primarily inside macrophages, and maintains persistent infection. In response to infection and inflammation, platelet activating factor C-16 (PAF C-16), a phospholipid compound, is released by various cells including neutophils and monocytes. We have recently shown that PAF C-16 can directly inhibit the growth of two representative non-pathogenic mycobacteria, Mycobacterium bovis BCG and Mycobacterium smegmatis (M. smegmatis), by damaging the bacterial cell membrane. Here, we have examined the effect of PAF C-16 on M. smegmatis residing within macrophages, and identified mechanisms involved in their growth inhibitory function. Our results demonstrated that exogenous PAF C-16 inhibited the growth of M. smegmatis inside phagocytic cells of monocytic cell line, THP-1; this effect was partially blocked by PAF receptor antagonists, suggesting the involvement of PAF receptor-mediated signaling pathways. Arachidonic acid, a downstream metabolite of PAF C-16 signaling pathway, directly inhibited the growth of M. smegmatis in vitro. Moreover, the inhibition of phospholipase C and phospholipase A 2 activities, involved in PAF C-16 signaling pathway, increased survival of intracellular M. smegmatis. Interestingly, we also observed that inhibition of inducible nitric oxide synthase (iNOS) enzyme and antibody-mediated neutralization of TNF-α partially mitigated the intracellular growth inhibitory effect of PAF C-16. Use of a number of PAF C-16 structural analogs, including Lyso-PAF, 2-O-methyl PAF, PAF C-18 and Hexanolamino PAF, revealed that the presence of acetyl group (CH 3 CO) at sn-2 position of the glycerol backbone of PAF is important for the intracellular growth inhibition activity against M. smegmatis. Taken together, these results suggest that exogenous PAF C-16 treatment inhibits intracellular M. smegmatis growth, at least partially, in a nitric oxide and TNF-α dependent manner.

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Section: Discussionmentioning

confidence: 88%