Published online before print September 27, 2001, doi: 10.1161/hh2201.099166
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2001 American Heart Association, Inc.
Molecular Medicine |
Leukocyte Integrin Mac-1 Recruits Toll/Interleukin-1 Receptor Superfamily Signaling Intermediates to Modulate NF-
B Activity
From the Cardiovascular Division (C.S., X.Z., Z.C., D.I.S.), Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass; and Celltech, Inc (M.K.R.), Slough, England.
Correspondence to Daniel I. Simon, MD, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis St, Tower 3, Boston, MA 02115. E-mail dsimon{at}rics.bwh.harvard.edu
Abstract—— The leukocyte integrin Mac-1 (
Mß2, CD11b/CD18) regulates important cell functions in inflammation, including adhesion, phagocytosis, and oxidative burst. Deficiency of Mac-1 reduces vessel wall inflammation and neointimal thickening after murine carotid artery injury. Although Mac-1 has been implicated in modulating AP-1 and NF-
B activity, the signal transduction pathways involved are undefined. cDNA array analysis of Mac-1–clustered compared with –nonclustered monocytic THP-1 cells showed increased expression of the signal transducer TRAF6 (TNF receptor–associated factor 6), leading us to consider the possibility that Mac-1 used a Toll/IL-1 receptor family–like signaling pathway. Mac-1–dependent activation of NF-B was potentiated by wild-type, and attenuated by dominant negative, TRAF6- and TGF-ß–activated kinase (TAK1) constructs. IRAK1 (IL-1 receptor associated kinase), a kinase immediately upstream of TRAF6, coimmunoprecipitated with Mac-1. Taken together, these observations indicate that Mac-1 recruits a Toll/IL-1 receptor family–like cascade to modulate NF-B activity. This represents a new pathway for integrin-dependent modulation of gene expression.
Key Words: leukocytes • integrins • signal transduction • gene expression
This article has been cited by other articles:
 |
|
 |
|
  K. Shimizu, P. Libby, R. Shubiki, M. Sakuma, Y. Wang, K. Asano, R. N. Mitchell, and D. I. Simon Leukocyte Integrin Mac-1 Promotes Acute Cardiac Allograft Rejection Circulation, April 15, 2008; 117(15): 1997 - 2008. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zirlik, C. Maier, N. Gerdes, L. MacFarlane, J. Soosairajah, U. Bavendiek, I. Ahrens, S. Ernst, N. Bassler, A. Missiou, et al. CD40 Ligand Mediates Inflammation Independently of CD40 by Interaction With Mac-1 Circulation, March 27, 2007; 115(12): 1571 - 1580. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Alvarez, J. I. F. Bass, J. R. Geffner, P. X. F. Calotti, M. Costas, O. A. Coso, R. Gamberale, M. E. Vermeulen, G. Salamone, D. Martinez, et al. Neutrophil Signaling Pathways Activated by Bacterial DNA Stimulation J. Immunol., September 15, 2006; 177(6): 4037 - 4046. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Wang, M. Sakuma, Z. Chen, V. Ustinov, C. Shi, K. Croce, A. C. Zago, J. Lopez, P. Andre, E. Plow, et al. Leukocyte Engagement of Platelet Glycoprotein Ib{alpha} via the Integrin Mac-1 Is Critical for the Biological Response to Vascular Injury Circulation, November 8, 2005; 112(19): 2993 - 3000. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. R. Curran, R. K. Morgan, P. J. Kingham, N. Durcan, W. G. McLean, M. T. Walsh, and R. W. Costello Mechanism of eosinophil induced signaling in cholinergic IMR-32 cells Am J Physiol Lung Cell Mol Physiol, February 1, 2005; 288(2): L326 - L332. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Chavakis, A. Athanasopoulos, J.-S. Rhee, V. Orlova, T. Schmidt-Woll, A. Bierhaus, A. E. May, I. Celik, P. P. Nawroth, and K. T. Preissner Angiostatin is a novel anti-inflammatory factor by inhibiting leukocyte recruitment Blood, February 1, 2005; 105(3): 1036 - 1043. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Flick, X. Du, and J. L. Degen Fibrin(ogen)-{alpha}M{beta}2 Interactions Regulate Leukocyte Function and Innate Immunity In Vivo Experimental Biology and Medicine, December 1, 2004; 229(11): 1105 - 1110. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Bajtay, C. Speth, A. Erdei, and M. P. Dierich Cutting Edge: Productive HIV-1 Infection of Dendritic Cells via Complement Receptor Type 3 (CR3, CD11b/CD18) J. Immunol., October 15, 2004; 173(8): 4775 - 4778. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Noubir, Z. Hmama, and N. E. Reiner Dual Receptors and Distinct Pathways Mediate Interleukin-1 Receptor-associated Kinase Degradation in Response to Lipopolysaccharide: INVOLVEMENT OF CD14/TLR4, CR3, AND PHOSPHATIDYLINOSITOL 3-KINASE J. Biol. Chem., June 11, 2004; 279(24): 25189 - 25195. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P Ballabh, M Simm, J Kumari, A N Krauss, A Jain, C Califano, M L Lesser, and S Cunningham-Rundles Neutrophil and monocyte adhesion molecules in bronchopulmonary dysplasia, and effects of corticosteroids Arch. Dis. Child. Fetal Neonatal Ed., January 1, 2004; 89(1): F76 - F83. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Levy, R. M. Jean-Jacques, C. Cywes, R. B. Sisson, K. A. Zarember, P. J. Godowski, J. L. Christianson, H.-K. Guttormsen, M. C. Carroll, A. Nicholson-Weller, et al. Critical Role of the Complement System in Group B Streptococcus-Induced Tumor Necrosis Factor Alpha Release Infect. Immun., November 1, 2003; 71(11): 6344 - 6353. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Ehlers, V. Ustinov, Z. Chen, X. Zhang, R. Rao, F. W. Luscinskas, J. Lopez, E. Plow, and D. I. Simon Targeting Platelet-Leukocyte Interactions: Identification of the Integrin Mac-1 Binding Site for the Platelet Counter Receptor Glycoprotein Ib{alpha} J. Exp. Med., October 6, 2003; 198(7): 1077 - 1088. [Abstract] [Full Text] [PDF]
|
|