Differential signal transduction, membrane trafficking, and immune effector functions mediated by FcγRI versus FcγRIIa

Dai, X. et al. (2009) Differential signal transduction, membrane trafficking, and immune effector functions mediated by FcγRI versus FcγRIIa. Blood, 114(2), pp. 318-327. (doi:10.1182/blood-2008-10-184457)

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Publisher's URL: http://dx.doi.org/10.1182/blood-2008-10-184457

Abstract

Receptors for the fragment crystallizable region of immunoglobulin-G (FcγRs) play an important role in linking the humoral and cellular arms of the immune response. In this study, we present a comprehensive functional comparison of 2 human Fc-receptors, FcγRI and FcγRIIa. Activation of FcγRI results in a novel signaling cascade that links phospholipase D1 to sphingosine kinase-1 in U937 cells and primary human monocytes. This induces the expression of proinflammatory mediators and is associated with trafficking of immune complexes into human leukocyte antigen-DM positive antigen-processing compartments coupled with improved MHC class II–mediated antigen presentation to T lymphocytes. In contrast, activation of FcγRIIa elicits signaling through phospholipase Cγ1, resulting in increases in intracellular calcium, activation of nicotinamide adenine dinucleotide phosphate-oxidative burst, and differential membrane trafficking combined with impaired antigen presentation and proinflammatory cytokine expression. These data provide a mechanistic insight into the disparate activities associated with Fc receptors in immunity, namely, reinforcement of immune responses through stimulation of proinflammatory signaling and antigen presentation, versus the maintenance of immunologic homeostasis through the noninflammatory clearance of immune complexes.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Melendez Romero, Dr Alirio
Authors: Dai, X., Jayapal, M., Tay, H. K., Reghunathan, R., Lin, G., Too, C. T., Lim, Y. T., Chan, S. H., Kemeny, D. M., Floto, R. A., Smith, K. G. C., Melendez, A. J., and MacAry, P. A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Blood
Publisher:American Society of Hematology
ISSN:0006-4971
ISSN (Online):1528-0020
Published Online:06 May 2009
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
462311Therapeutic potential of Sphingosine Kinase blockage in allergic anaphylaxis.Alirio Melendez RomeroMedical Research Council (MRC)G0700794Institute of Infection Immunity and Inflammation