Activation of NF-kappa B transcription factor in human neutrophils by sulphatides and L-selectin cross-linking.
Sulphated galactocerebroside (sulphatide) has been established as a ligand for L-selectin and shown to trigger intracellular signals in human neutrophils. We have found that sulphatide activated transcription factor NF-kappa B in human neutrophils in a concentration-dependent manner whereas non-sulphated galactocerebroside did not demonstrate such an effect. The activation was inhibitable by pretreatment with primary monoclonal anti-L-selectin antibody (clone LAM1-116). Binding of the primary antibody to L-selectin was insufficient to induce NF-kappa B activation but cross-linking of L-selectin with a secondary antibody was effective. alpha-Chymotrypsin, the agent known to shed L-selectin, activated NF-kappa B by itself. The response to sulphatides was inhibited by jasplakinolide, an actin-polymerising agent known to downregulate surface expression of L-selectin, Fc gamma RIIIb, CD43 and CD44. Recently we have reported that sulphatide stimulated the attachment of human neutrophils to collagen via Mac1 (CD11b/CD18) integrin [Sud'ina et al., Biochem. J. 359 (2001) 621-629]. We now show signalling from sulphatide to NF-kappa B activation and discuss its involvement in neutrophil adhesion.
Turutin
Denis V
DV
A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow 119992, Russia.
Kubareva
Elena A
EA
Pushkareva
Marina A
MA
Ullrich
Volker
V
Sud'ina
Galina F
GF
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002918:Chymotrypsin / Q000494:pharmacology; D047630:Depsipeptides; D024202:Electrophoretic Mobility Shift Assay; D005699:Galactosylceramides / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D019041:L-Selectin / Q000276:immunology / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D013433:Sulfoglycosphingolipids / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D047630:Depsipeptides; D005699:Galactosylceramides; D016328:NF-kappa B; D010456:Peptides, Cyclic; D013433:Sulfoglycosphingolipids; C057531:jasplakinolide; D019041:L-Selectin; D002918:Chymotrypsin; C117608:alpha-chymotrypsin