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

Abstract

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.