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Induction of human neutrophil chemotaxis by Candida albicans

Induction of human neutrophil chemotaxis by Candida albicans

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

"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 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; Gal▀1-4Glc-ceramide) but not NeuAc{alpha}2-3Gal▀1-4Glc▀1-1'-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{alpha}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." [Candida soluble ▀-D-glucan (CSBG)],

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Keywords: lactosylceramide lipid raft galactose neutrophil chemotaxis Candida albicans

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