The Journal of Immunology, Vol 148, Issue 4 1188-1196, Copyright © 1992 by American Association of Immunologists

ARTICLES

Stimulus-response coupling in monocytes infected with Leishmania. Attenuation of calcium transients is related to defective agonist- induced accumulation of inositol phosphates

M Olivier, KG Baimbridge and NE Reiner
Departments of Medicine, (Division of Infectious Diseases), University of British Columbia Faculty of Medicine, Vancouver, Canada.

Mononuclear phagocytes infected with Leishmania have been shown to have defective responses to extracellular stimuli. To investigate the potential relationship of these findings to alterations in calcium- dependent signaling pathways, the regulation of [Ca2+]i concentrations was examined in human peripheral blood monocytes infected with amastigotes of Leishmania donovani. Measurements of [Ca2+]i in fura-2- loaded monocytes were made at the single cell level by microfluorimetry. In normal monocytes, resting [Ca2+]i was 56 +/- 2 nM (mean +/- SEM). In contrast, in monocytes infected with Leishmania there was an approximately twofold increase in basal [Ca2+]i (122 +/- 5 nM, p less than 0.01 vs control). Treatment of cells with pertussis toxin before infection did not abrogate infection-induced increases in basal [Ca2+]i, suggesting that this effect was not mediated via the activation of a G protein coupled to phospholipase C. However, elevated resting [Ca2+]i did correlate with increased rates of 45Ca2+ uptake by infected monocytes. As expected, in response to treatment with 10(-7) M FMLP, control monocytes showed rapid net increases in [Ca2+]i of 303 +/- 19 nM. In contrast, net transients of [Ca2+]i in infected monocytes in response to FMLP were attenuated to only 137 +/- 9 nM (p less than 0.01 vs control). This result was not related to excess buffering of [Ca2+]i in infected cells as both control and infected monocytes showed equivalent transients of [Ca2+]i in response to the calcium ionophore A23187. Rather, inhibition of agonist-induced calcium release in infected cells appeared related to defective generation of second messenger because compared to control cells labeled with myo-[2- 3H]inositol, little accumulation of inositol 1,4,5-trisphosphate was detected in infected monocytes. Attenuation of inositol phosphate accumulation and calcium release in response to chemotactic peptide correlated with decreased FMLP-induced superoxide and hydrogen peroxide production by infected monocytes. These results provide direct evidence for defective regulation of [Ca2+]i and calcium-dependent signaling in Leishmania-infected monocytes and provide a basis for understanding abnormalities in activation-related responses that involve signaling through Ca(2+)-regulated pathways.

This article has been cited by other articles:

				F. F. Tuon, V. S. Amato, H. A. Bacha, T. AlMusawi, M. I. Duarte, and V. Amato Neto Toll-Like Receptors and Leishmaniasis Infect. Immun., March 1, 2008; 76(3): 866 - 872. [Full Text] [PDF]

				M. Bergeron and M. Olivier Trypanosoma cruzi-Mediated IFN-{gamma}-Inducible Nitric Oxide Output in Macrophages Is Regulated by iNOS mRNA Stability J. Immunol., November 1, 2006; 177(9): 6271 - 6280. [Abstract] [Full Text] [PDF]

				C. Leon, D. Nandan, M. Lopez, A. Moeenrezakhanlou, and N. E. Reiner Annexin V Associates with the IFN-{gamma} Receptor and Regulates IFN-{gamma} Signaling J. Immunol., May 15, 2006; 176(10): 5934 - 5942. [Abstract] [Full Text] [PDF]

				G. Forget, D. J. Gregory, and M. Olivier Proteasome-mediated Degradation of STAT1{alpha} following Infection of Macrophages with Leishmania donovani J. Biol. Chem., August 26, 2005; 280(34): 30542 - 30549. [Abstract] [Full Text] [PDF]

				M. Olivier, D. J. Gregory, and G. Forget Subversion Mechanisms by Which Leishmania Parasites Can Escape the Host Immune Response: a Signaling Point of View Clin. Microbiol. Rev., April 1, 2005; 18(2): 293 - 305. [Abstract] [Full Text] [PDF]

				L. Guizani-Tabbane, K. Ben-Aissa, M. Belghith, A. Sassi, and K. Dellagi Leishmania major Amastigotes Induce p50/c-Rel NF-{kappa}B Transcription Factor in Human Macrophages: Involvement in Cytokine Synthesis Infect. Immun., May 1, 2004; 72(5): 2582 - 2589. [Abstract] [Full Text] [PDF]

				K. R. Gantt, T. L. Goldman, M. L. McCormick, M. A. Miller, S. M. B. Jeronimo, E. T. Nascimento, B. E. Britigan, and M. E. Wilson Oxidative Responses of Human and Murine Macrophages During Phagocytosis of Leishmania chagasi J. Immunol., July 15, 2001; 167(2): 893 - 901. [Abstract] [Full Text] [PDF]

				M. KRESS and H. FICKENSCHER Infection by human varicella-zoster virus confers norepinephrine sensitivity to sensory neurons from rat dorsal root ganglia FASEB J, April 1, 2001; 15(6): 1037 - 1043. [Abstract] [Full Text] [PDF]

				S. Bhattacharyya, S. Ghosh, P. L. Jhonson, S. K. Bhattacharya, and S. Majumdar Immunomodulatory Role of Interleukin-10 in Visceral Leishmaniasis: Defective Activation of Protein Kinase C-Mediated Signal Transduction Events Infect. Immun., March 1, 2001; 69(3): 1499 - 1507. [Abstract] [Full Text] [PDF]

				D. Nandan, R. Lo, and N. E. Reiner Activation of Phosphotyrosine Phosphatase Activity Attenuates Mitogen-Activated Protein Kinase Signaling and Inhibits c-FOS and Nitric Oxide Synthase Expression in Macrophages Infected with Leishmania donovani Infect. Immun., August 1, 1999; 67(8): 4055 - 4063. [Abstract] [Full Text] [PDF]

				S. Corradin, J. Mauel, A. Ransijn, C. Sturzinger, and G. Vergeres Down-regulation of MARCKS-related Protein (MRP) in Macrophages Infected with Leishmania J. Biol. Chem., June 11, 1999; 274(24): 16782 - 16787. [Abstract] [Full Text] [PDF]

				S. Haque, H. Dumon, A. Haque, and L. H. Kasper Alteration of Intracellular Calcium Flux and Impairment of Nuclear Factor-AT Translocation in T Cells During Acute Toxoplasma gondii Infection in Mice J. Immunol., December 15, 1998; 161(12): 6812 - 6818. [Abstract] [Full Text] [PDF]

				M. Olivier, B.-J. Romero-Gallo, C. Matte, J. Blanchette, B. I. Posner, M. J. Tremblay, and R. Faure Modulation of Interferon-gamma -induced Macrophage Activation by Phosphotyrosine Phosphatases Inhibition. EFFECT ON MURINE LEISHMANIASIS PROGRESSION J. Biol. Chem., May 29, 1998; 273(22): 13944 - 13949. [Abstract] [Full Text] [PDF]

				D. V. Jovanovic, J. A. Di Battista, J. Martel-Pelletier, F. C. Jolicoeur, Y. He, M. Zhang, F. Mineau, and J.-P. Pelletier IL-17 Stimulates the Production and Expression of Proinflammatory Cytokines, IL-{beta} and TNF-{alpha}, by Human Macrophages J. Immunol., April 1, 1998; 160(7): 3513 - 3521. [Abstract] [Full Text] [PDF]

				R. Bernier, B. Barbeau, M. J. Tremblay, and M. Olivier The Lipophosphoglycan of Leishmania donovani Up-Regulates HIV-1 Transcription in T Cells Through the Nuclear Factor-{kappa}B Elements J. Immunol., March 15, 1998; 160(6): 2881 - 2888. [Abstract] [Full Text] [PDF]

				P. Sozzani, C. Cambon, N. Vita, M.-Hélèn. Séguélas, D. Caput, P. Ferrara, and B. Pipy Interleukin-13 Inhibits Protein Kinase C-triggered Respiratory Burst in Human Monocytes J. Biol. Chem., March 10, 1995; 270(10): 5084 - 5088. [Abstract] [Full Text] [PDF]