Activation of rat macrophages by Betafectin PGG-glucan requires cross-linking of membrane receptors distinct from complement receptor three (CR3).
PGG-glucan (Betafectin) is a soluble, highly purified yeast (1,3)-beta-glucan with broad anti-infective and immunomodulatory activities. These studies evaluated the ability of PGG-glucan to directly elicit O2- and tumor necrosis factor alpha (TNF-alpha) production by rat leukocytes in vitro. Particulate beta-glucan stimulated O2- production by the rat NR8383 alveolar macrophage cell line and resident rat peritoneal macrophages, but soluble PGG-glucan did not. In contrast, presentation of PGG-glucan to cells after covalent immobilization to a plastic surface caused a direct stimulation of O2- and TNF-alpha production. The O2- response of rat leukocytes to immobilized PGG-glucan was inhibited by soluble PGG-glucan, indicating that cellular responses to both immobilized and soluble PGG-glucan occur via common cell surface receptors. Because complement receptor type three (CR3) has been proposed as a beta-glucan receptor on human leukocytes, NR8383 cells were evaluated for the presence of CR3. Indirect immunofluorescence and flow cytometric analysis showed that despite being responsive to both particulate and immobilized beta-glucans, NR8383 cells expressed no detectable CR3. These results indicate that the beta-glucan receptors on NR8383 cells are not CR3 and suggest that physical presentation plays an important role in inducing pro-inflammatory leukocyte responses to PGG-glucan.
Michalek
M
M
Alpha-Beta Technology, Inc., Worcester, Massachusetts 01605, USA.
Melican
D
D
Brunke-Reese
D
D
Langevin
M
M
Lemerise
K
K
Galbraith
W
W
Patchen
M
M
Mackin
W
W
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D005936:Glucans / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects*; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D010969:Plastics; D051381:Rats; D017208:Rats, Wistar; D011971:Receptors, Immunologic / Q000378:metabolism*; D016897:Respiratory Burst / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000737:chemistry; D012995:Solubility; D013481:Superoxides / Q000378:metabolism; D013499:Surface Properties; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D047071:beta-Glucans
D000276:Adjuvants, Immunologic; D005936:Glucans; D016177:Macrophage-1 Antigen; D010969:Plastics; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D047071:beta-Glucans; C045268:beta-glucan receptor; D013481:Superoxides; C033363:beta-1,3-glucan