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ß-glucan affects leukocyte navigation in a complex chemotactic gradient

      Abstract

      Background

      Polymorphonuclear leukocytes (PMNs) must traverse endogenous chemotactic gradients (interleukin 8 [IL-8]) before reaching target chemoattractants (fMLP [N-formylmethionine-leucine-phenylalanine], C5a) produced at a site of bacterial infection. Complement receptor 3 (CR3; CD11b/CD18) contains 2 distinct binding sites, one that mediates adhesion and a lectin-like domain (LLD) that binds polysaccharides of microbial origin. This laboratory previously reported an increase in the chemotactic capacity of PMNs toward fMLP upon ligation of the CR3 LLD with β-glucan, a CR3 agonist. Current studies sought to determine the effect of β-glucan on PMN navigation toward other chemoattractants alone and in a competing chemotactic environment.

      Methods

      Migration was assessed by serum agarose overlay with the use of chambered slides containing or not, β-glucan. Migration of human PMNs at 37°C for 2 hours was evaluated toward C5a or IL-8 alone and in competing gradients. Selected groups were treated with anti-CR3–blocking antibodies. The number of chemotactic cells was quantified by microscopy.

      Results

      β-glucan significantly enhanced chemotaxis toward C5a and suppressed that toward IL-8 in a CR3-dependent fashion. In the competing chemotactic gradient assays (C5a vs IL-8), β-glucan further enhanced migration toward C5a while not affecting that toward IL-8.

      Conclusions

      β-glucan selectively upregulates PMN chemotaxis toward C5a while suppressing chemotaxis toward IL-8.
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