Gram-Negative Bacteria Salmonella typhimurium Boost Leukotriene Synthesis Induced by Chemoattractant fMLP to Stimulate Neutrophil Swarming.

Leukotriene synthesis in neutrophils is critical for host survival during infection. In particular, leukotriene B ₄ (LTB ₄ ) is a powerful neutrophil chemoattractant that plays a crucial role in neutrophil swarming. In this work, we demonstrated that preincubation of human neutrophils with Salmonella typhimurium strongly stimulated LTB ₄ production induced by the bacterial chemoattractant, peptide N-formyl-L-methionyl-L-leucyl-l-phenylalanine (fMLP), while the reverse sequence of additions was ineffective. Preincubation with bacterial lipopolysaccharide or yeast polysaccharide zymosan particles gives weaker effect on fMLP-induced LTB ₄ production. Activation of 5-lipoxygenase (5-LOX), a key enzyme in leukotrienes biosynthesis, depends on rise of cytosolic concentration of Ca ²⁺ and on translocation of the enzyme to the nuclear membrane. Both processes were stimulated by S. typhimurium . With an increase in the bacteria:neutrophil ratio, the transformation of LTB ₄ to ω-OH-LTB ₄ was suppressed, which further supported increased concentration of LTB ₄ . These data indicate that in neutrophils gathered around bacterial clusters, LTB ₄ production is stimulated and at the same time its transformation is suppressed, which promotes neutrophil swarming and elimination of pathogens simultaneously.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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