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| IJCEM Copyright © 2008-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711 |
Int J Clin Exp Med 2011;4(4):320-330
Original Article
Role of myeloid-specific G-protein coupled receptor kinase-2 insepsis
Sitaram Parvataneni, Babu Gonipeta, Nandakumar Packiriswamy, Taehyung Lee, Haritha Durairaj, Narayanan Parameswaran
Department of Physiology, Michigan State University, East Lansing, MI; Graduate program in Comparative Medicine and Integrative
Biology, Michigan State University, East Lansing, MI, USA.
Received October 21, 2011; accepted November 5, 2011, 2011; Epub November 9, 2011; Published November 30, 2011
Abstract: Previous studies have implicated a critical role for G-protein coupled receptor kinase-2 (GRK2) in sepsis owing to its ability to
regulate inflammatory response and chemotaxis of immune cells. We therefore, hypothesized that deletion of GRK2 in myeloid cells
would significantly modulate the pathogenesis of polymicrobial sepsis. To test this hypothesis, we induced cecal ligation and puncture
(CLP), in mice with myeloid-specific deletion of GRK2 and the correspondingGRK2 wild type littermates and determined the
inflammatory response (IL-6 and IL-10), immune cell infiltration, bacterial load and survival. Six hours after surgery, plasmaIL-6 and
IL-6:IL-10 ratios weresignificantly enhanced in the GRK2 knockouts compared to the GRK2 wild type mice. Compared to these
effects,IL-6was significantly elevatedin the bronchoalveolar lavage but not in the peritoneal fluid of theGRK2 knockout mice.On the other
hand, peritoneal IL-10 was significantly elevated in the GRK2 knockout mice compared to the GRK2 wild type. Even though GRK2
knockout mice exhibited an exaggerated cytokine response, there was no difference in immune cell infiltration into the primary site of
infection or in bacterial clearance when compared between the GRK2 wild typeand GRK2 knockout miceafter surgery. Furthermore, in
spite of the enhanced pro-inflammatory profile early after surgery, there was only amodest increase in mortality in the GRK2
knockoutcompared to the GRK2 wild typemice after CLP. Together, our studies demonstrate that myeloid-specific knockout of GRK2
renders the mice more susceptible to an early pro-inflammatory state. However, myeloid-specific GRK2 is not involved in immune cell
infiltration to the primary site of infection or in bacterial clearance and does not significantly modulate mortality in the cecal ligation
puncture model of polymicrobial sepsis. (IJCEM1110006).
Key words: G-protein coupled receptor kinase-2 (GRK2), inflammation, sepsis, GRK2 knockout mice
Full Text PDF
Address all correspondence to:
Dr. Narayanan Parameswaran
Department of Physiology
Michigan State University
East Lansing, MI 48824, USA.
Tel: 517-884-5115
E-mail: paramesw@msu.edu
Original Article
Role of myeloid-specific G-protein coupled receptor kinase-2 insepsis
Sitaram Parvataneni, Babu Gonipeta, Nandakumar Packiriswamy, Taehyung Lee, Haritha Durairaj, Narayanan Parameswaran
Department of Physiology, Michigan State University, East Lansing, MI; Graduate program in Comparative Medicine and Integrative
Biology, Michigan State University, East Lansing, MI, USA.
Received October 21, 2011; accepted November 5, 2011, 2011; Epub November 9, 2011; Published November 30, 2011
Abstract: Previous studies have implicated a critical role for G-protein coupled receptor kinase-2 (GRK2) in sepsis owing to its ability to
regulate inflammatory response and chemotaxis of immune cells. We therefore, hypothesized that deletion of GRK2 in myeloid cells
would significantly modulate the pathogenesis of polymicrobial sepsis. To test this hypothesis, we induced cecal ligation and puncture
(CLP), in mice with myeloid-specific deletion of GRK2 and the correspondingGRK2 wild type littermates and determined the
inflammatory response (IL-6 and IL-10), immune cell infiltration, bacterial load and survival. Six hours after surgery, plasmaIL-6 and
IL-6:IL-10 ratios weresignificantly enhanced in the GRK2 knockouts compared to the GRK2 wild type mice. Compared to these
effects,IL-6was significantly elevatedin the bronchoalveolar lavage but not in the peritoneal fluid of theGRK2 knockout mice.On the other
hand, peritoneal IL-10 was significantly elevated in the GRK2 knockout mice compared to the GRK2 wild type. Even though GRK2
knockout mice exhibited an exaggerated cytokine response, there was no difference in immune cell infiltration into the primary site of
infection or in bacterial clearance when compared between the GRK2 wild typeand GRK2 knockout miceafter surgery. Furthermore, in
spite of the enhanced pro-inflammatory profile early after surgery, there was only amodest increase in mortality in the GRK2
knockoutcompared to the GRK2 wild typemice after CLP. Together, our studies demonstrate that myeloid-specific knockout of GRK2
renders the mice more susceptible to an early pro-inflammatory state. However, myeloid-specific GRK2 is not involved in immune cell
infiltration to the primary site of infection or in bacterial clearance and does not significantly modulate mortality in the cecal ligation
puncture model of polymicrobial sepsis. (IJCEM1110006).
Key words: G-protein coupled receptor kinase-2 (GRK2), inflammation, sepsis, GRK2 knockout mice
Full Text PDF
Address all correspondence to:
Dr. Narayanan Parameswaran
Department of Physiology
Michigan State University
East Lansing, MI 48824, USA.
Tel: 517-884-5115
E-mail: paramesw@msu.edu
