The Journal of Immunology, Vol 150, Issue 10 4571-4580, Copyright © 1993 by American Association of Immunologists

ARTICLES

Lectin-like inhibition of immune complex receptor-mediated stimulation of neutrophils. Effects on cytosolic calcium release and superoxide production

G Sehgal, K Zhang, RF Todd 3d, LA Boxer and HR Petty
Department of Biological Sciences, Wayne State University, Detroit, MI 48202.

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-.

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