Lysosomal enzyme release from human monocytes by particulate activators is mediated by beta-glucan inhibitable receptors.
Human peripheral blood monocytes ingest particulate activators and generate leukotrienes via a trypsin-sensitive, beta-glucan-inhibitable receptor. The incubation of monolayers of monocytes with from 4 X 10(5) to 2 X 10(8) zymosan or glucan particles resulted in a dose-dependent release of up to 9% +/- 1.9 and 17.8% +/- 5.3 (mean +/- SD, n = 3) of the lysosomal enzyme, N-acetylglucosaminidase, into the culture medium. Lysosomal enzyme release occurred throughout the 2-hr period studied, with the greatest rate of N-acetyl-glucosaminidase release occurring during the first hour; the presence of 5 micrograms/ml of cytochalasin B accelerated this process when zymosan was the agonist. The preincubation of monocytes with from 0.5 to 500 micrograms/ml of soluble yeast beta-glucan inhibited N-acetylglucosaminidase release by 4 X 10(7) zymosan and glucan particles in a dose-dependent manner, with 50% inhibition occurring with 50 micrograms/ml of soluble yeast beta-glucan (mean +/- SD, n = 3). Preincubation with as much as 5 mg/ml of yeast mannan had no inhibitory effect on N-acetylglucosaminidase release. The pretreatment for 30 min of monolayers of monocytes with 50 micrograms/ml of affinity-purified trypsin, which selectively inactivates the monocyte-phagocytic response to particulate activators, also fully inhibited lysosomal enzyme release induced by zymosan and glucan particles. The inhibitory effects of a soluble ligand, yeast beta-glucan, and of trypsin pretreatment on lysosomal enzyme release correspond to the inhibitory effect of these agents on monocyte phagocytosis of zymosan and glucan particles and thus indicates ligand specificity for the beta-glucan receptor in the release of stored intracellular mediators.
D000118:Acetylglucosaminidase / Q000378:metabolism; D003170:Complement Pathway, Alternative; D004305:Dose-Response Relationship, Drug; D005936:Glucans / Q000494:pharmacology; D006801:Humans; D008247:Lysosomes / Q000201:enzymology; D009000:Monocytes / Q000201:enzymology*; D010587:Phagocytosis; D011956:Receptors, Cell Surface / Q000502:physiology*; D011971:Receptors, Immunologic; D012636:Secretory Rate / Q000187:drug effects; D012995:Solubility; D014357:Trypsin; D015054:Zymosan / Q000494:pharmacology
D005936:Glucans; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C045268:beta-glucan receptor; D015054:Zymosan; D000118:Acetylglucosaminidase; D014357:Trypsin