Lectin-like inhibition of immune complex receptor-mediated stimulation of neutrophils. Effects on cytosolic calcium release and superoxide production.
We have tested the role of lectin-like interactions, with particular emphasis on CR3, in insoluble immune complex (IC)-mediated activation of human polymorphonuclear leukocytes (PMN). The ability of IC to trigger intracellular Ca2+ release and O2- production by normal PMN, saccharide-treated cells, and CR3-deficient PMN (leukocyte adhesion deficiency, LAD, patients) were tested. When indo-1-labeled normal PMN were stimulated with IC in Ca(2+)-free buffer, intracellular Ca2+ rose from approximately 100 nM to approximately 230 nM. However, when LAD PMN were tested, a small rise in intracellular Ca2+ was observed. Because previous studies have shown that certain saccharides inhibit CR3-Fc gamma RIII co-capping, we tested a panel of saccharides to determine their ability to influence IC-mediated intracellular Ca2+ release. When normal PMN were exposed to 0.15 M N-acetyl-D-glucosamine (NADG), D-mannose, or alpha-methyl-mannoside, the Ca2+ response to IC was significantly reduced. However, addition of 0.15 M glucose, raffinose, sucrose, galactose, fructose, or sorbitol did not significantly affect the Ca2+ response, suggesting that the response was specific for certain saccharides. To test the physiologic consequences of these Ca2+ signals, we have examined the ability of saccharides to influence O2- production by normal PMN and the ability of LAD PMN to produce O2- upon triggering by IC. Normal PMN stimulated with IC generated 4.3 +/- 1.7 nmol/10(6) cells/30 min of O2-. In contrast, O2- production was inhibited by 0 to 20% by glucose, galactose, sucrose, sorbitol, fructose, and raffinose and > or = 50% by NADG and mannose. LAD PMN, which display diminished Ca2+ signals, were found to produce O2- at 47 +/- 6% of control levels. NADG and mannose dose-response studies indicated that they cooperatively block O2-.
Sehgal
G
G
Department of Biological Sciences, Wayne State University, Detroit, MI 48202.
Zhang
K
K
Todd
R F
RF
Boxer
L A
LA
Petty
H R
HR
D000328:Adult; D000936:Antigen-Antibody Complex / Q000276:immunology*; D015703:Antigens, CD / Q000378:metabolism; D018821:CD18 Antigens; D002118:Calcium / Q000502:physiology*; D002448:Cell Adhesion; D006801:Humans; D066298:In Vitro Techniques; D037102:Lectins / Q000494:pharmacology*; D016177:Macrophage-1 Antigen / Q000502:physiology*; D009504:Neutrophils / Q000276:immunology*; D009844:Oligosaccharides / Q000494:pharmacology; D011940:Receptor Aggregation / Q000187:drug effects; D017452:Receptors, IgG / Q000502:physiology*; D016897:Respiratory Burst; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism*
D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D018821:CD18 Antigens; D037102:Lectins; D016177:Macrophage-1 Antigen; D009844:Oligosaccharides; D017452:Receptors, IgG; D013481:Superoxides; D002118:Calcium