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In vitro inhibition of group B streptococcus-induced polymorphonuclear leukocyte aggregation
Abstract:
Evidence suggests that part of the pathophysiologic response seen in group B streptococcal (GBS) sepsis may be due to polymorphonuclear leukocyte (PMN) activation. Indomethacin (INDO), which inhibits eicosanoid metabolism, attenuates the pathophysiologic response stimulated by GBS, possibly due to inhibition of PMN aggregation. We examined the capability of two eicosanoid metabolism inhibitors, INDO and nordihydroguaiaretic acid (NDGA), to inhibit PMN aggregation induced by heat-inactivated opsonized GBS and GBS-activated plasma. Opsonized GBS-induced PMN aggregation was inhibited by INDO (50-500 microM) and NDGA (1-100 microM). Over similar concentration ranges, INDO and NDGA had no significant effect on PMN aggregation induced by GBS-activated plasma. PMNs in plasma aggregate in response to unopsonized GBS. The stimuli for aggregation are opsonized GBS and GBS-activated plasma. INDO (50-500 microM) was unable to inhibit aggregation under this condition. Over the same concentration range in which INDO inhibited opsonized GBS-induced PMN aggregation, INDO was unable to inhibit opsonized GBS-induced superoxide production in PMNs. NDGA was examined but was found to interfere with the assay. The above evidence suggests PMN aggregation via eicosanoid metabolism may play a role in GBS-induced sepsis, which may be attenuated by agents such as INDO and NDGA.
Insights
Indomethacin and NDGA inhibit polymorphonuclear leukocyte (PMN) aggregation during Group B Streptococcus (GBS) sepsis. These findings suggest eicosanoid metabolism inhibitors may treat GBS sepsis by reducing PMN aggregation.
Area of Science:
- Immunology
- Microbiology
- Pharmacology
Background:
- Group B Streptococcus (GBS) sepsis involves polymorphonuclear leukocyte (PMN) activation.
- Eicosanoid metabolism inhibitors, like Indomethacin (INDO), may attenuate GBS-induced pathophysiologic responses by inhibiting PMN aggregation.
Purpose of the Study:
- To investigate the ability of eicosanoid metabolism inhibitors, INDO and nordihydroguaiaretic acid (NDGA), to inhibit PMN aggregation induced by GBS.
- To determine if these inhibitors affect PMN aggregation induced by GBS-activated plasma.
Main Methods:
- Assessed PMN aggregation induced by heat-inactivated opsonized GBS and GBS-activated plasma.
- Tested the effects of varying concentrations of INDO and NDGA on PMN aggregation.
- Measured PMN superoxide production to assess other inflammatory responses.
Main Results:
- INDO and NDGA significantly inhibited PMN aggregation induced by opsonized GBS.
- Neither INDO nor NDGA affected PMN aggregation induced by GBS-activated plasma.
- INDO did not inhibit opsonized GBS-induced superoxide production in PMNs; NDGA interfered with the assay.
Conclusions:
- PMN aggregation mediated by eicosanoid metabolism appears to play a role in GBS-induced sepsis.
- Agents like INDO and NDGA may offer therapeutic potential for GBS sepsis by modulating PMN aggregation.