Published online before print May 2, 2006

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0106069

Received for publication January 31, 2006.

Accepted for publication March 7, 2006.

Article

Induction of human neutrophil chemotaxis by Candida albicans-derived -1,6-long glycoside side-chain-branched -glucan

Tadashi Sato ^*, Kazuhisa Iwabuchi ^*@, Isao Nagaoka , Yoshiyuki Adachi ^¶, Naohito Ohno ^¶, Hiroshi Tamura ^||, Kuniaki Seyama , Yoshinosuke Fukuchi , Hitoshi Nakayama ^*, Fumiko Yoshizaki ^*, Kenji Takamori ^*, and Hideoki Ogawa ^*

*Institute for Environmental and Gender-Specific Medicine, Departments of Respiratory Medicine and Host Defense and Biochemical Research, Juntendo University Graduate School of Medicine, Tokyo, Japan; Laboratory of Biochemistry, Juntendo University School of Health Care and Nursing, Chiba, Japan; ^¶Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Japan; and ^||Seikagaku Corporation, Tokyo, Japan

^@ To whom correspondence should be addressed. E-mail: iwabuchi{at}med.juntendo.ac.jp.

Abstract

Polysaccharide -1,3-D-glucans (-glucans) are components of the cell wall of various fungi and show immunomodulatory activities. -Glucans have been reported to enhance neutrophil accumulation during pathogenic fungi-induced lung inflammation. Therefore, we examined whether -glucans themselves possess chemotactic activities for human neutrophils. Among several kinds of -glucans, -1,6-long glucosyl side-chain-branched -glucan, isolated from Candida albicans [Candida soluble -D-glucan (CSBG)], dose-dependently induced neutrophil migration in a Boyden chamber system. In contrast, 1,6-monoglucosyl-branched -glucans, such as Sparassis crispa-derived -glucan (SCG) and grifolan (GRN), which were derived from nonpathogenic fungi, hardly induced neutrophil migration. Moreover, CSBG-induced neutrophil migration was inhibited completely by liposomes containing neutral glycosphingolipid lactosylceramide (LacCer; Gal1-4Glc-ceramide) but not NeuAc2-3Gal1-4Glc1-1`-Cer ganglioside. Furthermore, binding experiments demonstrated that CSBG bound to glycosphingolipids (such as LacCer) with a terminal galactose residue; however, SCG and GRN (1,6-monoglucosyl-branched -glucans) did not bind to LacCer. It is important that a Src kinase inhibitor protein phosphatase 1, a phosphatidylinositol-3 kinase (PI-3K) inhibitor wortmannin, and a G_i/o inhibitor pertussis toxin inhibited neutrophil migration toward CSBG. Taken together, our results suggest that -1,6-long glucosyl side-chain-branched -glucan CSBG binds to LacCer and induces neutrophil migration through the activation of Src family kinase/PI-3K/heterotrimeric G-protein signal transduction pathways.

Key Words: lactosylceramide • grifolan • galactosyl ceramide

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