Lipopolysaccharide-induced gelatinase granule mobilization primes neutrophils for activation by galectin-3 and formylmethionyl-Leu-Phe

We have earlier shown that galectin-3, a lactose-binding mammalian lectin t hat is secreted from activated macrophages, basophils, and mast cells, indu ces activation of the NADPH oxidase in exudated but not in peripheral blood neutrophils (A. Karlsson, P. Follin, H. Leffler, and C. Dahlgren, Blood 91 :3430-3438, 1998). The alteration in responsiveness occurring during extrav asation correlated with mobilization of the gelatinase and/or specific gran ules to the cell surface, indicating a role for mobilizable galectin-3 rece ptors. In this study we have investigated galectin-3-induced NADPH oxidase activation, measured as superoxide production, in lipopolysaccharide (LPS)- primed neutrophils. Upon galectin-3 challenge, the LPS-primed cells produce d superoxide, both extracellularly and intracellularly. A primed extracellu lar response to formyl methionyl-Leu-Phe (fMLF) was also achieved. The expo sure of complement receptors 1 and 3 as well as the formyl peptide receptor on the cell surface was markedly increased after LPS treatment, indicating that granule fusion with the plasma membrane had occurred. Further assessm ent of specific markers for neutrophil granules showed that the LPS treatme nt had mobilized the gelatinase granules but only a minor fraction of the s pecific granules. We thus suggest that the mechanism behind LPS priming lie s at the level of granule (receptor) mobilization for galectin-3 as well as for fMLF.