Differential regulation by leukotrienes and calcium of Fc gamma receptor-induced phagocytosis and Syk activation in dendritic cells versus macrophages.
Macrophage (MØ) phagocytosis via the Fc receptor for immunoglobulin G (Fc gammaR) requires the spleen tyrosine kinase (Syk) and serves an important antimicrobial function. We have reported previously that Fc gammaR-mediated ingestion and Syk activation in MØ are amplified by and depend on the proinflammatory lipid mediator leukotriene B4 (LTB4). Although Fc gammaR-mediated ingestion is also important for antigen uptake, there is no information about LTB4 regulation of these processes in dendritic cells (DCs). In this study, we compared murine bone marrow (BM)-derived DCs to MØ from BM, peritoneum, and the pulmonary alveolar space. Neither phagocytosis nor Syk activation in DCs was influenced by exogenous LTB4. Unlike the various MØ populations, Syk activation in DCs was likewise unaffected by pharmacologic or genetic strategies to inhibit endogenous LTB4 synthesis or to block the high-affinity LTB4 receptor BLT1. DCs were refractory to regulation by LTB4 despite the fact that they expressed BLT1 and mobilized intracellular calcium in response to its ligation. This resistance to LTB4 in DCs instead reflected the fact that in contrast to MØ, Syk activation in DCs was itself entirely independent of calcium. These results identify a fundamental difference in Fc gammaR signaling between DCs and MØ, which may relate to the divergent, functional consequences of target ingestion in the two cell types.
Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor, MI 48109-0642, USA.
Claudio
C
Canetti
David M
DM
Aronoff
Mun
M
Choe
Nicolas
N
Flamand
Scott
S
Wettlaufer
Galen B
GB
Toews
Gwo-Hsiao
GH
Chen
Marc
M
Peters-Golden
D000818:Animals; D017951:Antigen Presentation; D001854:Bone Marrow Cells / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D004912:Erythrocytes; D006918:Hydroxyurea / Q000031:analogs & derivatives / Q000494:pharmacology; D007074:Immunoglobulin G / Q000276:immunology; D007211:Indoles / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D051379:Mice; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D009895:Opsonin Proteins / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects* / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D017452:Receptors, IgG / Q000502:physiology*; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors; D012756:Sheep; D000072377:Syk Kinase; D002722:Chlorobenzenes
D006918:Hydroxyurea; D007074:Immunoglobulin G; D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins; D007975:Leukotriene B4; D009895:Opsonin Proteins; D011505:Protein-Tyrosine Kinases; D058919:Purinergic P2 Receptor Antagonists; D017452:Receptors, IgG; D018102:Receptors, Leukotriene B4; D000072377:Syk Kinase; C513241:Ltb4r protein, rat; C503704:Ltb4r1 protein, mouse; C060893:MK-886; D002722:Chlorobenzenes; C000606897:Syk protein, mouse; C000606898:Syk protein, rat; C063449:zileuton