Inhibition of Complement Activation with EDTA <i>in Vivo</i> during Sham Hemodialysis

Kandus, A.; Benedik, M; Bren, Andrej; Drinovec, Jože; Fliser, Danilo; Knap, Bojan; Kladnik, S.; Ivanovich, Peter

doi:10.1177/039139889101400810

Cited by 2 publications

(2 citation statements)

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“…We employed normal human serum to drive THP-1 differentiation/adherence in the absence of exogenous THP-1 activators like PMA. Also, in the absence of the ability to genetically ablate complement activity as with C3 −/− mouse serum, we instead generated complement-deficient human serum through physical heat inactivation (heat-inactivated human sera, hiHS) or chemical inhibition with ethylenediaminetetraacetic acid (NHS + EDTA) ( 61 , 62 ). Notably, neither heat inactivation nor EDTA supplementation is toxic to THP-1 cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Anaphylatoxin signaling activates macrophages to control intracellular Rickettsia proliferation

Dahmani,

Zhu,

Cook

et al. 2023

Microbiol Spectr

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Pathogenic Rickettsia species proliferate within the cytoplasm of permissive host cells in vivo . The cytoplasm of these host cells is adequate to support the complex metabolic and physiological needs for Rickettsia growth. However, a dramatic host/pathogen interplay occurs when Rickettsia encounter innate immune cells, whereby the bacteria can proliferate as normal or the host can restrict bacterial growth. This interplay is most divergent within myeloid host cells, where intra- and extracellular factors can produce either successful Rickettsia parasitism or innate immune control of bacterial proliferation. With the prior knowledge that the mammalian complement system is activated during mammalian infection, we sought to determine if extracellular complement activation and anaphylatoxin signaling can modify the fate of Rickettsia within mononuclear host cells. Results indicate that supplementation of growth media with either C3a or C5a anaphylatoxin peptides is sufficient for many myeloid cells to control the proliferation of multiple different Rickettsia species. Chemical or genetic disruption of anaphylatoxin signaling or anaphylatoxin receptors eliminates complement-induced restriction of bacterial proliferation. Finally, anaphylatoxin signaling modifies macrophage physiology by inducing inflammatory phenotypes that ultimately control the intracellular proliferation of these pathogens. IMPORTANCE Pathogenic Rickettsia species are extremely dangerous bacteria that grow within the cytoplasm of host mammalian cells. In most cases, these bacteria are able to overpower the host cell and grow within the protected environment of the cytoplasm. However, a dramatic conflict occurs when Rickettsia encounter innate immune cells; the bacteria can “win” by taking over the host, or the bacteria can “lose” if the host cell efficiently fights the infection. This manuscript examines how the immune complement system is able to detect the presence of Rickettsia and alert nearby cells. Byproducts of complement activation called anaphylatoxins are signals that “activate” innate immune cells to mount an aggressive defensive strategy. This study enhances our collective understanding of the innate immune reaction to intracellular bacteria and will contribute to future efforts at controlling these dangerous infections.

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Section: Resultsmentioning

confidence: 99%

“…Pooled NHS was purchased from Innovative Research. NHS was heat-inactivated at 56°C for 30 min or with 20 mM EDTA where noted ( 62 , 167 ). NMS (C57BL/6J) and C3 −/− MS were isolated by cardiac puncture and Z-gel (Sarstedt) centrifugation.…”

Section: Methodsmentioning

confidence: 99%