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The role of ceramide of human macrophage gangliosides in activation of human macrophages
Author(s) -
Berenson Charles S.,
Gallery Melissa A.,
Smigiera Jane M.,
Rasp Robin H.
Publication year - 2002
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.72.3.492
Subject(s) - ceramide , biology , macrophage , microbiology and biotechnology , lipid signaling , immunology , biochemistry , inflammation , apoptosis , in vitro
Gangliosides of macrophages have immunoregulatory and structural attributes, distinct from neural gangliosides. We previously produced a monoclonal antibody to human macrophage gangliosides (HMG; mAb25F4), which inhibited macrophage migration and recognized a surface‐accessible epitope. We investigated expanded immunoregulatory properties and molecular domains for antibody recognition. mAb25F4 directly induced human macrophage production of proinflammatory cytokines, interleukin‐1β, and tumor necrosis factor α. Conditions were established for selective, reversible depletion of HMG with D‐ threo ‐(R, R)‐1‐phenyl‐2‐decanoyl‐amino‐3‐morpholine‐1‐propa‐nol. mAb25F4 had diminished recognition for ganglioside‐depleted macrophages, which was restored with regeneration of gangliosides. Although desialylation of HMG did not impair mAb25F4 recognition, enzymatic cleavage of ceramide abolished antibody binding. Antibody recognition was specific for the ceramide fraction, with preferential recognition or ceramide of HMG and murine macrophage gangliosides and limited recognition for neural tissue ceramide and gangliosides. This study underscores the importance of structurally distinct ceramide of macrophage gangliosides as a critical domain for ganglioside‐mediated activation of human macrophages.