Modulation of lipopolysaccharide-induced monocyte activation by heparin-binding protein and fucoidan

Activated polymorphonuclear leukocytes release heparin-binding protein (HBP ; also known as CAP37 or azurocidin) from azurophilic granules. HBP is a st rong chemoattractant for monocytes that also prolongs monocyte survival and potentiates endotoxin (lipopolysaccharide [LPS])-induced production of tum or necrosis factor alpha (TNF-alpha). We investigated the binding of fluore scein isothiocyanate-conjugated HBP to human monocytes in the presence of E DTA and the polysaccharide fucoidan. EDTA, which chelates divalent cations, has been widely used to study the role of divalent cations in receptor-lig and interactions or enzyme activity. Fucoidan has been used to inhibit the binding of various ligands to scavenger receptors or selectins. Scavenger r eceptors are multiligand receptors that mediate endocytosis of proteases, p rotease-inhibitor complexes, lipoproteins, and LPS-lipid A. Fucoidan also i nterferes with leukocyte rolling by binding to L-selectins (expressed on le ukocytes) and P-selectins (expressed on platelets and endothelium). We demo nstrate that the binding of the neutrophil-derived protein HBP to monocytes is inhibited in the presence of EDTA and fucoidan. In addition, fucoidan a nd EDTA abrogate the enhancing effect of HBP on LPS-induced TNF-alpha produ ction. These data provide supporting evidence that HBP binds to a receptor expressed on monocytes. This receptor is dependent on divalent cations and is possibly related to the scavenger receptor. Furthermore, we demonstrate that fucoidan, by itself, stimulates TNF-alpha release from isolated monocy tes in a CD14-independent fashion. This is an important finding for the int erpretation of results from studies that use fucoidan to "block" either sca venger receptors or L- or P-selectins.