Research Abstract
ß-glucan Affects Leukocyte Navigation
in a Complex Chemotactic Gradient
Vassiliki L. Tsikitis, MD, Jorge E. Albina, MD, and Jonathan S. Reichner, PhD, Providence, RI
From the Department of Surgery, Rhode Island Hospital and Brown Medical School, Providence, RI
Surgery 2004;136:384-9.
Background. Polymorphonuclear leukocytes (PMNs) must traverse endogenous chemotactic gradients (interleukin 8 [IL-8]) before reaching target chemoattractants (fMLP [N-formylmethionine leucinephenylalanine], 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 378C for 2 hours was evaluated toward C5a or IL-8 alone and in competing gradients. Selected groups were treated with anti-CR3eblocking 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. (Surgery 2004;136:384-9.)