PMID- 16501050 OWN - NLM STAT- MEDLINE DCOM- 20060626 LR - 20161128 IS - 0741-5400 (Print) IS - 0741-5400 (Linking) VI - 79 IP - 5 DP - 2006 May TI - Coupling of C3bi to IgG inhibits the tyrosine phosphorylation signaling cascade downstream Syk and reduces cytokine induction in monocytes. PG - 1073-82 AB - The effect of coupling C3bi to immunoglobulin G (IgG) immune complexes (IC) on their ability to produce protein tyrosine phosphorylation and activation of the mitogen-activated protein kinase (MAPK) and the Akt/protein kinase B (PKB) routes was assessed in human monocytes. Cross-linking Fc receptors for IgG activated the protein tyrosine kinase Syk, phospholipases Cgamma1 and Cgamma2, the MAPK cascade, and the Akt/PKB route. Linkage of C3bi to the gamma-chain of IgG produced a decrease of the protein bands displaying tyrosine phosphorylation, whereas the MAPK cascades and the Akt/PKB route remained almost unaffected. Zymosan particles, which because of their beta-glucan content mimic the effect of fungi, produced a limited increase of tyrosine-phosphorylated protein bands, whereas treatment of zymosan under conditions adequate for C3bi coating increased its ability to induce protein tyrosine phosphorylation. Noteworthy, this was also observed under conditions where other components of serum might be bound by zymosan particles, for instance, serum IgG, thereby suggesting their potential involvement in Syk activation. The induction of cytokines showed a changing pattern consistent with the changes observed in the signaling pathways. IC induced monocyte chemoattractant protein-1 (MCP-1)/CC chemokine ligand 2 (CCL2), interleukin (IL)-1beta, and eotaxin-2/CCL24, which were not observed with C3bi-coated IC. Zymosan induced the expression of tumor necrosis factor alpha (TNF-alpha), TNF-beta, IL-10, IL-6, and MCP-2/CCL8, whereas the cytokine signature of C3bi-coated zymosan also included interferon-inducible protein 10/CXC chemokine ligand 10, platelet-derived growth factor-BB, and I-309/CCL1. Taken together, these findings indicate that C3bi targets the phagocytic cargo, and engagement or diversion of the Syk route determines the phagocyte response. FAU - Trinidad, Antonio Garcia AU - Trinidad AG AD - Instituto de Biologia y Genetica Molecular, Consejo Superior de Investigaciones Cientificas and Universidad de Valladolid, Spain. FAU - de la Puerta, Maria Luisa AU - de la Puerta ML FAU - Fernandez, Nieves AU - Fernandez N FAU - Bayon, Yolanda AU - Bayon Y FAU - Crespo, Mariano Sanchez AU - Crespo MS FAU - Alonso, Andres AU - Alonso A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060224 PL - England TA - J Leukoc Biol JT - Journal of leukocyte biology JID - 8405628 RN - 0 (Cytokines) RN - 0 (Immunoglobulin G) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Macromolecular Substances) RN - 0 (beta-Glucans) RN - 42HK56048U (Tyrosine) RN - 80295-43-8 (Complement C3b) RN - 9010-72-4 (Zymosan) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.2 (SYK protein, human) RN - EC 2.7.10.2 (Syk Kinase) RN - EC 2.7.11.1 (Oncogene Protein v-akt) RN - EC 3.1.4.3 (Phospholipase C gamma) SB - IM MH - Cell Line MH - Complement C3b/*immunology/metabolism MH - Cytokines/drug effects/*metabolism MH - Down-Regulation/drug effects/immunology MH - Feedback, Physiological/immunology MH - Humans MH - Immunoglobulin G/*metabolism MH - Intracellular Signaling Peptides and Proteins/*immunology/metabolism MH - MAP Kinase Signaling System/drug effects/physiology MH - Macromolecular Substances/immunology/metabolism MH - Monocytes/drug effects/*immunology/metabolism MH - Oncogene Protein v-akt/metabolism MH - Phagocytosis/drug effects/*immunology MH - Phospholipase C gamma/metabolism MH - Phosphorylation/drug effects MH - Protein-Tyrosine Kinases/*immunology/metabolism MH - Signal Transduction/drug effects/immunology MH - Syk Kinase MH - Tyrosine/metabolism MH - Zymosan/pharmacology MH - beta-Glucans/pharmacology EDAT- 2006/02/28 09:00 MHDA- 2006/06/27 09:00 CRDT- 2006/02/28 09:00 PHST- 2006/02/28 09:00 [pubmed] PHST- 2006/06/27 09:00 [medline] PHST- 2006/02/28 09:00 [entrez] AID - jlb.1205701 [pii] AID - 10.1189/jlb.1205701 [doi] PST - ppublish SO - J Leukoc Biol. 2006 May;79(5):1073-82. doi: 10.1189/jlb.1205701. Epub 2006 Feb 24.