Lipoteichoic acids selectively stimulate rat mast cells to cysteinyl leukotriene generation and affect mast cell migration after tumor necrosis factor (TNF)-priming

It is well established that mast cells play a critical role in the host defense against bacteria. Upon stimulation with bacteria and their antigens, mast cells release various mediators and cytokines that promote the development of inflammation at the site of infection. In the present study, we examined the ability of lipoteichoic acids (LTAs), some of the major components of cell walls of most gram-positive bacteria, to stimulate mast cell degranulation and histamine release as well as to generate of cysteinyl leukotrienes (LTs). We also studied the influence of LTAs on mast cell migration. Experiments were done on rat peritoneal mast cells and LTA from Staphyloccocus aureus and LTA from Bacillus subtilis were used. We have stated that neither S. aureus LTA nor B. subtilis LTA used at a wide range of concentrations (from 10 −4 to 105 ng/mL) induced mast cell degranulation and histamine release. However, stimulation of mast cells with both LTAs resulted in generation and release of significant levels of LTs. We have also documented that none of the LTAs stimulated rat mast cell migration, even in the presence of laminin. IL-6 priming did not influence mast cell migration towards LTAs, whereas, pretreatment of mast cells with TNF caused time-dependent mast cell migration in response to LTAs stimulation. Pretreatment of mast cells with anti-TNFR1 antibodies completely inhibited LTA-induced migratory response of TNF-primed mast cells. Our results showed that LTAs might be among important bacterial antigens involved in mast cell activation during bacterial infections.