This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Song, X. Articles by Lee, S. C. Search for Related Content PubMed PubMed Citation Articles by Song, X. Articles by Lee, S. C.

 Previous Article  |  Next Article 

Infection and Immunity, September 2002, p. 5177-5184, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.5177-5184.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Fc Receptor I- and III-Mediated Macrophage Inflammatory Protein 1 Induction in Primary Human and Murine Microglia

Departments of Pathology,¹ Cell Biology,² Pediatrics,³ Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461⁴

Received 8 March 2002/ Returned for modification 19 April 2002/ Accepted 4 June 2002

Microglial cell phagocytic receptors may play important roles in the pathogenesis and treatment of several neurological diseases. We studied microglial Fc receptor (FcR) activation with respect to the specific FcR types involved and the downstream signaling events by using monoclonal antibody (MAb)-coated Cryptococcus neoformans immune complexes as the stimuli and macrophage inflammatory protein 1 (MIP-1) production as the final outcome. C. neoformans complexed with murine immunoglobulin G (IgG) of 1, 2a, and 3, but not 2b isotype, was effective in inducing MIP-1 in human microglia. Since murine 2b binds to human FcRII (but not FcRI or FcRIII), these results indicate that FcRI and/or FcRIII is involved in MIP-1 production. Consistent with this, an antibody that blocks FcRII (IV.3) failed to inhibit MIP-1 production, while an antibody that blocks FcRIII (3G8) did. An anti-C. neoformans MAb, 18B7 (IgG1), but not its F(ab')₂, induced extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase kinase phosphorylation, and MIP-1 release was suppressed by the ERK inhibitor U0126. C. neoformans plus 18B7 also induced degradation of I-B, and MIP-1 release was suppressed by the antioxidant NF-B inhibitor pyrrolidine dithiocarbamate. To confirm the role of FcR more directly, we isolated microglia from wild-type and various FcR-deficient mice and then challenged them with C. neoformans plus 18B7. While FcRII-deficient microglia showed little difference from the wild-type microglia, both FcRI -chain- and FcRIII -chain-deficient microglia produced less MIP-1, and the common Fc -chain-deficient microglia showed no MIP-1 release. Taken together, our results demonstrate a definitive role for FcRI and FcRIII in microglial chemokine induction and implicate ERK and NF-B as the signaling components leading to MIP-1 expression. Our results delineate a new mechanism for microglial activation and may have implications for central nervous system inflammatory diseases.

Editor: S. H. E. Kaufmann

This article has been cited by other articles:

• Maglione, P. J., Xu, J., Casadevall, A., Chan, J. (2008). Fc{gamma} Receptors Regulate Immune Activation and Susceptibility during Mycobacterium tuberculosis Infection. J. Immunol. 180: 3329-3338 [Abstract] [Full Text]  
• Johnson, E. C., Jia, L., Cepurna, W. O., Doser, T. A., Morrison, J. C. (2007). Global Changes in Optic Nerve Head Gene Expression after Exposure to Elevated Intraocular Pressure in a Rat Glaucoma Model. IOVS 48: 3161-3177 [Abstract] [Full Text]  
• Lister, K. J., Hickey, M. J. (2006). Immune complexes alter cerebral microvessel permeability: roles of complement and leukocyte adhesion. Am. J. Physiol. Heart Circ. Physiol. 291: H694-H704 [Abstract] [Full Text]  
• Mednick, A. J., Nosanchuk, J. D., Casadevall, A. (2005). Melanization of Cryptococcus neoformans Affects Lung Inflammatory Responses during Cryptococcal Infection. Infect. Immun. 73: 2012-2019 [Abstract] [Full Text]  
• Ichiyama, T., Ueno, Y., Hasegawa, M., Ishikawa, Y., Matsubara, T., Furukawa, S. (2005). Intravenous immunoglobulin does not increase Fc{gamma}RIIB expression on monocytes/macrophages during acute Kawasaki disease. Rheumatology (Oxford) 44: 314-317 [Abstract] [Full Text]  
• Qin, H., Edberg, J. C., Gibson, A. W., Page, G. P., Teng, L., Kimberly, R. P. (2004). Differential Gene Expression Modulated by the Cytoplasmic Domain of Fc{gamma}RIa (CD64) {alpha}-Chain. J. Immunol. 173: 6211-6219 [Abstract] [Full Text]  
• Rock, R. B., Gekker, G., Hu, S., Sheng, W. S., Cheeran, M., Lokensgard, J. R., Peterson, P. K. (2004). Role of Microglia in Central Nervous System Infections. Clin. Microbiol. Rev. 17: 942-964 [Abstract] [Full Text]  
• Song, X., Tanaka, S., Cox, D., Lee, S. C. (2004). Fc{gamma} receptor signaling in primary human microglia: differential roles of PI-3K and Ras/ERK MAPK pathways in phagocytosis and chemokine induction. J. Leukoc. Biol. 75: 1147-1155 [Abstract] [Full Text]  
• He, W., Casadevall, A., Lee, S. C., Goldman, D. L. (2003). Phagocytic Activity and Monocyte Chemotactic Protein Expression by Pulmonary Macrophages in Persistent Pulmonary Cryptococcosis. Infect. Immun. 71: 930-936 [Abstract] [Full Text]