Dectin-1-mediated MR shedding is dependent on Syk and partially on Raf-1, utilizes the Akt-independent PI3K pathway, and is not affected by the presence of an agonist for TLR2. Thio-Mφ preincubated for 1 h with Syk kinase inhibitor IV (A), Raf-1 inhibitor I (B), wortmannin (C), or Akt inhibitor VI (D) were treated with particulate β-glucan (β-Gluc; 50 particles/cell) for 3 h at 37 °C in the presence of inhibitors. cMR and sMR levels were assessed in cell lysates and supernatants, respectively, by Western blot analysis as described under “Experimental Procedures.” Thio-Mφ were treated with Pam3-Cys-Ser-Lys4 (10 μg/ml) in the presence or absence of particulate β-glucan (50 particles/cell) for 3 h at 37 °C (E). cMR and sMR levels were assessed in cell lysates and supernatants. Data are representative of three independent experiments. Unt, untreated.