Beta-glucan affects leukocyte navigation in a complex chemotactic gradient.
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 beta-glucan, a CR3 agonist. Current studies sought to determine the effect of beta-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, beta-glucan. Migration of human PMNs at 37 degrees 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
beta-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), beta-glucan further enhanced migration toward C5a while not affecting that toward IL-8.


CONCLUSIONS
beta-glucan selectively upregulates PMN chemotaxis toward C5a while suppressing chemotaxis toward IL-8.
Department of Surgery, Rhode Island Hospital and Brown Medical School, Providence, RI 02903, USA.
Vassiliki L
VL
Tsikitis
Jorge E
JE
Albina
Jonathan S
JS
Reichner
D002465:Cell Movement / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D015936:Complement C5a / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005936:Glucans / Q000494:pharmacology*; D006801:Humans; D016209:Interleukin-8 / Q000502:physiology; D037102:Lectins; D016177:Macrophage-1 Antigen / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology
D005936:Glucans; D016209:Interleukin-8; D037102:Lectins; D016177:Macrophage-1 Antigen; D015936:Complement C5a