Irma Bernatchez-Lemaire, Ph.D.

Professor

Affiliation
CMM, RGN, room 3131

Research Interests
Keywords

Inflammation, macrophages, cytokines, macrophage fusion, macrophage activation, purinergic P2X7 receptor, extracellular ATP, anti-inflammatory H4-related peptides

Degrees

BSc., Université de Sherbrooke, Québec
PhD, Université Laval, Québec
Post-doctoral fellow: University of California Medical Center, San Francisco, CA
Post-doctoral fellow: Columbia University, New York, NY

Contact info:

RGN, 451 Smyth Road, Rm 3131, Ottawa ON K1H8M5
Phone: 562-5800 x8361
Fax:
Email: ilemaire@uottawa.ca

Research Interests

Our long term research interest is to elucidate the cellular and molecular mechanisms regulating macrophage differentiation and activation in chronic inflammation. Macrophage recruitment and plasticity are key components of several chronic disorders including various autoimmune diseases (Crohn’s disease, rheumatoid arthritis, multiple sclerosis, autoimmune hepatitis), atherosclerosis, fibrotic diseases, obesity, type 2 diabetes, asthma and cancer. There is an increasing burden of chronic inflammatory disease in aging societies with escalating health costs and human suffering across the globe. Understanding the mechanisms that regulate macrophage phenotypic plasticity in tissues is critical for the identification and validation of markers and therapeutic targets in inflammatory conditions.

Our research is focused on two major aspects:

Purinergic signaling in macrophage fusion and the formation of multinucleated giant cells, a hallmark of chronic inflammation.

This area of research concerns the underlying mechanisms that regulate macrophage fusion to form multinucleated giant cells. We showed the physiological/pathological relevance of the purinergic P2X7 receptor for extracellular ATP as a critical effector of MA fusion in response to the inflammatory cytokine GM-CSF. Recently, we have identified a new P2X7/ATP/Adenosine signaling pathway critical for efficient promotion of macrophage fusion. Our data also provided the first evidence for the participation of the hemichannel protein Pannexin-1 in this process. We are presently investigating the requirement of P2X7-dependent pore formation for cell fusion and ATP release, and the role of Pannexin-1 in cell fusion.

The P2X7 as a crucial switch for activation of pro-inflammatory macrophages and a relevant target for the control of inflammation.

Of paramount importance for the control of dysregulated inflammatory responses is the understanding of the signal(s) required to switch macrophages into a pro-inflammatory state. Stimulation of the P2X7 receptor in macrophages is linked to activation of the inflammasome and production of inflammatory cytokines and mediators including IL-1, IL-6, IL-8 and MMP-9. Work from our laboratory suggests that the P2X7 receptor may represent an amplification pathway for inflammation. Interestingly, we have identified a class of H4-related peptides that interfere with P2X7-mediated functions in vitro and in vivo. We are investigating the mechanisms of action of these peptides at the P2X7 receptor level.

Selected Publications:

Lemaire I., Falzoni S., Adinolfi A. Purinergic signaling in giant cell formation. Frontiers in Biosciences (Elite. Ed.), 4: 41-55, 2012

Lemaire I. Falzoni S., Zhang B., Pellegatti P., Di Virgilio F. The P2X7 receptor and Pannexin-1 are both required for the promotion of Multinucleated Macrophages by the Inflammatory Cytokine GM-CSF. J. Immunol. 187: 3878-3887, 2011

Pellegatti P., Falzoni S, Donvito G. Lemaire I., Di Virgilio F. P2X7 receptor drives osteoclast fusion by increasing the extracellular adenosine concentration. FASEB J. 25: 1264-1274, 2011.

Lemaire I., Falzoni S., Leduc N., Zhang B., Pellegatti, Chiozzi P, Adinolfi E.,Di Virgilio F. Involvement of the purinergic P2X7 receptor in the formation of multinucleated giant cells. J. Immunol., 177, 7257-7265, 2006 (cover, November 15, issue).

Di Virgilio F., Lemaire I. Purinergic signalling in inflammation and immunomodulation. CRC Reviews., “Nucleotides and Regulation of Bone Cell Function”, eds. G. Burnstock and T.R. Arnett, Taylor & Francis, pp. 159-193, Oct. 2006.

Poirier R., Lemaire I., Lemaire S. Characterization, localization and possible anti- inflammatory function of rat histone H4 mRNA variants. FEBS J., 273, 4360-4373, 2006

René Poirier, Irma Lemaire, Michel Dumont, Natacha Leduc, Hoang-Thanh Le, Simon Lemaire. Correlation between the expression of the histone H4 mRNA variant H4-v.1 and the levels of histone H4 -(86B100) and H4-(89B102)(OGP) in various rat tissues and alveolar macrophages. Peptides, 26,1503-1511 2005

Le H.T., Lemaire I.., Gilbert A.K., Jolicoeur F., Yang L., Leduc N.,Lemaire S. Histogranin-like antinociceptive and anti-inflammatory derivatives of o-phenylenediamine and benzimidazole.J. Pharmacol. Exp. Ther., 309 , 146-155, 2004.

Le H.T., Lemaire I.., Gilbert A.K., Jolicoeur F., Lemaire S. Bioactive peptidic analogues and cyclostereoisomers of minimal antinociceptive Histogranin fragment-(7-10).J. Medicinal Chem., 46, 3094-3101, 2004.

Lemaire I., Leduc N. Characterization of purinergic P2X7 receptor function in lung alveolar macrophages: bidirectional regulation by Th1/Th2 cytokines. Drug Dev. Res., 59, 118-127, 2003.

Lemaire I., Yang H., Lafont V., Dornand J., Commes T., Cantin M.-F. Differential effects of M-CSF and GM-CSF on cytokine gene expression during alveolar macrophage differentiation into multinucleated giant cells (MGC): Role for IL-6 in Type 2 MGC formation. J. Immunol., 157, 5118-5125, 1996.

Lemaire I., Yang H., Lauzon W., Gendron N. M-CSF and GM-CSF promote alveolar macrophage differentiation into multinucleated giant cells with distinct phenotypes. J. Leukoc. Biol., 60, 509-518, 1996.

Lemaire I., Ouellet S. Role of transforming growth factor-ß1 in down-regulating TNF production by alveolar macrophages during asbestos-induced pulmonary fibrosis. Mediators Inflammation, 5, 37-42, 1996.

Publications:

Refereed Articles: 91 ( see Lemaire I. website of Science; Scopus; Pubmed)
Refereed Abstracts (111)

Lemaire I., Yang H. Colony stimulating factors induce alveolar macrophage differentiation and giant cell formation. Ann. N.Y. Acad. Sci., 297-309, 1996.

Lemaire S., Rogers C., Dumont M., Shukla V.K., Lapierre C., Prasad J., Lemaire I. Histogranin, a modified histone H4 fragment endowed with N-methyl-D-aspartate antagonist and immunostimulatory activities. Life Sciences, 56, 1233-1241, 1995.

Lemaire I., Yang H., Cantin MF., Lemaire S. Regulation of cytokine production in alveolar macrophages by histogranin, a novel endogenous pentadecapeptide. Immunol. Letters, 41, 37-42, 1994.

Lemaire I., Cantin MF., Lemaire S. Phencyclidine (PCP)-like peptide, histogranin, modulates cell-mediated immune function. Regul. Peptides, Suppl. 1, S261-S262, 1994.

Lauzon W., Lemaire I. Alveolar macrophage inhibition of lung-associated NK activity: involvement of prostaglandins and transforming growth factor-β. Exp. Lung Res., 20, 331-349, 1994.

Yang H., McLeese J., Weisbart M., Dionne JL., Lemaire I., Aubin RA. Simplified high throughput protocol for Northern hybridization. Nucleic Acids Res., 21, 3337-3338, 1993.

Lemaire S., Griffiths J., Lapierre C., Lemaire I., Merali Z., Ravindran AV. Characterization of histogranin receptors in human peripheral blood lymphocytes. Biochem. Biophys. Res. Commun., 194, 1323-1329, 1993.

Ouellet S., Yang H., Aubin RA, Hawley RG, Lemaire I. Bidirectional modulation of TNF-α production by alveolar macrophages in asbestos-induced pulmonary fibrosis. J. Leuk. Biol., 53, 279-286, 1993.

Yang H., Lauzon W., Lemaire I. Effects of hyperthermia on natural killer cells. Inhibition of lytic function and microtubule organization. Int. J. Hyperthermia, 8, 87-97, 1992.

Lemaire I. Bombesin-related peptides modulate interleukin-1 production by alveolar macrophages. Neuropeptides, 20, 217-223, 1991.

Lauzon W., Lemaire I. Effects of biological response modifiers on lung natural killer activity. Immunopharmacol. Immunotoxicol., 13, 237-250, 1991.

Lemaire I., Jones S., Khan F. Bombesin-like peptides in alveolar macrophage : increased release in pulmonary inflammation and fibrosis. Neuropeptides, 20, 63-72, 1991.

Lemaire I. Selective differences in macrophage populations and monokine production in resolving pulmonary granuloma and fibrosis. Am. J. Pathol., 138, 487-495, 1991.

Lauzon W., Yang H., Lemaire I. Comparative analysis of natural killer function in lung, spleen and peripheral blood lymphocytes : evidence of differential characteristics. Regional Immunol., 3, 145-150, 1991.

Lemaire I., St-Jean M. Modulation of lung-associated natural killer activity by resident and activated alveolar macrophages. Immunol. Invest., 19, 27-40, 1990.

Laplante C., Lemaire I. Interactions between alveolar macrophage subpopulations modulate their migratory function. Am. J. Pathol., 136, 199-206, 1990.

Lemaire I. Neurotensin enhances interleukin-1 production by activated alveolar macrophage. J. Immunol., 140, 2983-2988, 1988

Rola-Pleszczynski M., Chavaillaz P.-A., Lemaire I. Stimulation of interleukin 2 and interferon gamma production by leukotriene B4 in human lymphocyte cultures. Prostaglandins, Leukotrienes and Medicine, 23, 207-210, 1986.

Lemaire I., Beaudoin H., Massé S., Grondin C. Alveolar macrophage stimulation of lung fibroblast growth in asbestos-induced pulmonary fibrosis. Am. J. Pathol., 122, 205-211, 1986.

Rola-Pleszczynski M., Lemaire I. Leukotrienes augment interleukin-1 production by human monocytes. J. Immunol., 135, 3958-3961, 1985.

Lemaire I., Dubois C. In vitro suppression of fibroblast growth inhibitory lymphokine production by asbestos. Clin. Exp. Immunol., 53, 239-248, 1983.

Lemaire I., Rola-Pleszczynski M., Bégin R. Asbestos exposure enhances the release of fibroblast growth factor by sheep alveolar macrophages. J. Reticuloendothel. Soc., 33, 275-285, 1983.

Rola-Pleszczynski M., Lieu H., Hamel J., Lemaire I. Stimulated human lymphocytes produce a soluble factor which inhibits fibroblast migration. Cell. Immunology, 74, 104-100, 1982.

Lemaire S., Livett B., Tseng R., Mercier P., Lemaire I. Studies on the inhibitory action of opiate compounds in isolated bovine adrenal chromaffin cells : non-involvement of stereospecific opiate binding sites. J. Neurochemistry, 36, 886-392.

Lemaire S., Derome G., Tseng R., Mercier P., Lemaire I. Distinct regulations by calcium of cyclic GMP levels and catecholamine secretion in isolated bovine adrenal chromaffin cells. Metabolism, 30, 462-468,

Lemaire S., Lemaire I., Dean D.M., Livett B.G. Opiate receptors and adrenal medullary function. Nature, 288, 303-304, 1980.

Lemaire I., Tseng ER., Lemaire S. Systemic administration of B-endorphin : Potent Hypotensive Effect involving a Serotonergic Pathway. Proc. Natl. Acad. Sci. USA, 75, 6240-6242, 1978.

Lemaire I., Coffino P. Coexpression of Mutant and Wild Type Protein Kinase in lymphoma cells resistant to dibutytyl cyclic AMP. J. Cellular Physiology, 92, 437-446, 1977.

Lemaire I., Coffino P. Cyclic AMP-induced cytolysis in S49 Cells: Selection of an Unresponsive “Deathless” Mutant. Cell, 11, 149-155, 1977.

Scholarships and Awards

Scientist and professor :

CIHR-CNR International Award for Invited Scientist, Universita di Ferrara, Italy
MRC-INSERM International Award for Invited Scientist, Université Montpellier, France
MRC Scholar, University of Ottawa
FRSQ (Fonds de la Recherche en Santé du Québec) Scholar, Université de Sherbrooke
Recognition Award for Outstanding Contribution to Medical Education, Faculty of Medicine, University of Ottawa
Award of Excellence, Faculty of Medicine, University of Ottawa

postdoctoral:

MRC postdoctoral fellowship, University of California, San Francisco Medical Center, USA
MRC postdoctoral fellowship, Columbia University, New York, USA