© 2000 American Heart Association, Inc.
Integrative Physiology |
A Role for Platelets and Endothelial Selectins in Tumor Necrosis Factor-
–Induced Leukocyte Recruitment in the Brain Microvasculature
From the Immunology Research Group (J.C.-T., M.J.H., P.K.), University of Calgary, Calgary, Alberta, and Division of the Intensive Care, Department of Pediatrics (J.H.); Department of Laboratory Medicine (J.M.); and Department of Cellular and Molecular Medicine (I.T.S.), University of Ottawa, Ontario, Canada.
Correspondence to Dr Paul Kubes, Immunology Research Group, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1, Canada. E-mail pkubes{at}ucalgary.ca
Abstract—The
mechanisms mediating leukocyte recruitment into the cerebral nervous
system during inflammation are still poorly understood. The objective
of this study was to investigate the leukocyte recruitment in the brain
microcirculation by intravital microscopy. Superfusion of the brain
with artificial cerebrospinal fluid did not induce leukocyte rolling or
adhesion. However, intraperitoneal tumor necrosis factor-
(TNF-)
caused marked leukocyte rolling and adhesion in the brain
microcirculation. Histology revealed that the recruitment was primarily
of neutrophils. Both E- and P-selectin were required for
TNF-–induced leukocyte recruitment, as rolling was reduced after
treatment with either anti–E- or anti–P-selectin antibody and
eliminated in E- or P-selectin–deficient mice. A significant increase
in brain P- and E-selectin expression was seen after TNF- treatment,
but both were an order of magnitude less than in any other tissue. We
observed significant platelet paving of TNF-–stimulated endothelium
and found that anti-platelet antibody reduced leukocyte rolling and
adhesion, as did acetylsalicylic acid (aspirin). However, depletion of
platelets did not reduce cerebral P-selectin expression. Moreover,
chimeric mice lacking P-selectin on endothelium but not platelets had
significantly decreased P-selectin expression and reduced leukocyte
recruitment in the brain. This suggests a role for endothelial
P-selectin in cerebral leukocyte recruitment. In conclusion,
TNF-–induced neutrophil recruitment into the brain requires both
endothelial E-selectin and P-selectin as well as platelets, but
platelet P-selectin was not a major contributor to this
process.
Key Words: selectin • tumor necrosis factor- • neutrophil • inflammation • cerebral
This article has been cited by other articles:
 |
|
 |
|
  M. U. Norman, W. G. James, and M. J. Hickey Differential roles of ICAM-1 and VCAM-1 in leukocyte-endothelial cell interactions in skin and brain of MRL/faslpr mice J. Leukoc. Biol., July 1, 2008; 84(1): 68 - 76. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Drevets, J. E. Schawang, M. J. Dillon, M. R. Lerner, M. S. Bronze, and D. J. Brackett Innate Responses to Systemic Infection by Intracellular Bacteria Trigger Recruitment of Ly-6Chigh Monocytes to the Brain J. Immunol., July 1, 2008; 181(1): 529 - 536. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Kerfoot, G. Andonegui, C. S. Bonder, and L. Liu Exogenous stromal cell-derived factor-1 induces modest leukocyte recruitment in vivo Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2524 - H2534. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. D. Wagner and P. S. Frenette The vessel wall and its interactions Blood, June 1, 2008; 111(11): 5271 - 5281. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Petri, M. Phillipson, and P. Kubes The Physiology of Leukocyte Recruitment: An In Vivo Perspective J. Immunol., May 15, 2008; 180(10): 6439 - 6446. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. McDonald, E. F. McAvoy, F. Lam, V. Gill, C. de la Motte, R. C. Savani, and P. Kubes Interaction of CD44 and hyaluronan is the dominant mechanism for neutrophil sequestration in inflamed liver sinusoids J. Exp. Med., April 14, 2008; 205(4): 915 - 927. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Tailor, K. C. Wood, J. L. Wallace, R. D. Specian, and D. N. Granger Roles of platelet and endothelial cell COX-1 in hypercholesterolemia-induced microvascular dysfunction Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3636 - H3642. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Liu, K. D. Puri, J. M. Penninger, and P. Kubes Leukocyte PI3K{gamma} and PI3K{delta} have temporally distinct roles for leukocyte recruitment in vivo Blood, August 15, 2007; 110(4): 1191 - 1198. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ishikawa, E. Sekizuka, N. Yamaguchi, H. Nakadate, S. Terao, D. N. Granger, and H. Minamitani Angiotensin II type 1 receptor signaling contributes to platelet-leukocyte-endothelial cell interactions in the cerebral microvasculature Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2306 - H2315. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. M. Chandrasekharan, M. Siemionow, M. Unsal, L. Yang, E. Poptic, J. Bohn, K. Ozer, Z. Zhou, P. H. Howe, M. Penn, et al. Tumor necrosis factor {alpha} (TNF-{alpha}) receptor-II is required for TNF-{alpha}-induced leukocyte-endothelial interaction in vivo Blood, March 1, 2007; 109(5): 1938 - 1944. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zhou, B. M. Lapointe, S. R. Clark, L. Zbytnuik, and P. Kubes A Requirement for Microglial TLR4 in Leukocyte Recruitment into Brain in Response to Lipopolysaccharide J. Immunol., December 1, 2006; 177(11): 8103 - 8110. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J. Lister and M. J. Hickey Immune complexes alter cerebral microvessel permeability: roles of complement and leukocyte adhesion Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H694 - H704. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Bonder, S. R. Clark, M. U. Norman, P. Johnson, and P. Kubes Use of CD44 by CD4+ Th1 and Th2 lymphocytes to roll and adhere Blood, June 15, 2006; 107(12): 4798 - 4806. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Kuligowski, A. R. Kitching, and M. J. Hickey Leukocyte Recruitment to the Inflamed Glomerulus: A Critical Role for Platelet-Derived P-Selectin in the Absence of Rolling. J. Immunol., June 1, 2006; 176(11): 6991 - 6999. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Kerfoot, M. U. Norman, B. M. Lapointe, C. S. Bonder, L. Zbytnuik, and P. Kubes Reevaluation of P-Selectin and {alpha}4 Integrin as Targets for the Treatment of Experimental Autoimmune Encephalomyelitis J. Immunol., May 15, 2006; 176(10): 6225 - 6234. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. S. Bonder, M. U. Norman, T. MacRae, P. R. Mangan, C. T. Weaver, D. C. Bullard, D.-M. McCafferty, and P. Kubes P-Selectin Can Support Both Th1 and Th2 Lymphocyte Rolling in the Intestinal Microvasculature Am. J. Pathol., December 1, 2005; 167(6): 1647 - 1660. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Andonegui, S. M. Kerfoot, K. McNagny, K. V. J. Ebbert, K. D. Patel, and P. Kubes Platelets express functional Toll-like receptor-4 Blood, October 1, 2005; 106(7): 2417 - 2423. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Piccio, B. Rossi, L. Colantonio, R. Grenningloh, A. Gho, L. Ottoboni, J. W. Homeister, E. Scarpini, M. Martinello, C. Laudanna, et al. Efficient Recruitment of Lymphocytes in Inflamed Brain Venules Requires Expression of Cutaneous Lymphocyte Antigen and Fucosyltransferase-VII J. Immunol., May 1, 2005; 174(9): 5805 - 5813. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Liu, D. C. Cara, J. Kaur, E. Raharjo, S. C. Mullaly, J. Jongstra-Bilen, J. Jongstra, and P. Kubes LSP1 is an endothelial gatekeeper of leukocyte transendothelial migration J. Exp. Med., February 7, 2005; 201(3): 409 - 418. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Kerfoot, E. M. Long, M. J. Hickey, G. Andonegui, B. M. Lapointe, R. C. O. Zanardo, C. Bonder, W. G. James, S. M. Robbins, and P. Kubes TLR4 Contributes to Disease-Inducing Mechanisms Resulting in Central Nervous System Autoimmune Disease J. Immunol., December 1, 2004; 173(11): 7070 - 7077. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. M. Lapointe, L. M. Herx, V. Gill, L. M. Metz, and P. Kubes IVIg therapy in brain inflammation: etiology-dependent differential effects on leucocyte recruitment Brain, December 1, 2004; 127(12): 2649 - 2656. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. C. O. Zanardo, C. S. Bonder, J. M. Hwang, G. Andonegui, L. Liu, D. Vestweber, L. Zbytnuik, and P. Kubes A down-regulatable E-selectin ligand is functionally important for PSGL-1-independent leukocyte-endothelial cell interactions Blood, December 1, 2004; 104(12): 3766 - 3773. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Tavener, E. M. Long, S. M. Robbins, K. M. McRae, H. Van Remmen, and P. Kubes Immune Cell Toll-Like Receptor 4 Is Required for Cardiac Myocyte Impairment During Endotoxemia Circ. Res., October 1, 2004; 95(7): 700 - 707. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Cara, K. V. J. Ebbert, and D.-M. McCafferty Mast Cell-Independent Mechanisms of Immediate Hypersensitivity: A Role for Platelets J. Immunol., April 15, 2004; 172(8): 4964 - 4971. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kerschensteiner, C. Stadelmann, B. S. Buddeberg, D. Merkler, F. M. Bareyre, D. C. Anthony, C. Linington, W. Bruck, and M. E. Schwab Targeting Experimental Autoimmune Encephalomyelitis Lesions to a Predetermined Axonal Tract System Allows for Refined Behavioral Testing in an Animal Model of Multiple Sclerosis Am. J. Pathol., April 1, 2004; 164(4): 1455 - 1469. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Nishijima, J. Kiryu, A. Tsujikawa, K. Miyamoto, M. Honjo, H. Tanihara, A. Nonaka, K. Yamashiro, H. Katsuta, S. Miyahara, et al. Platelets Adhering to the Vascular Wall Mediate Postischemic Leukocyte-Endothelial Cell Interactions in Retinal Microcirculation Invest. Ophthalmol. Vis. Sci., March 1, 2004; 45(3): 977 - 984. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Kivisakk, D. J. Mahad, M. K. Callahan, C. Trebst, B. Tucky, T. Wei, L. Wu, E. S. Baekkevold, H. Lassmann, S. M. Staugaitis, et al. Human cerebrospinal fluid central memory CD4+ T cells: Evidence for trafficking through choroid plexus and meninges via P-selectin PNAS, July 8, 2003; 100(14): 8389 - 8394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Battistini, L. Piccio, B. Rossi, S. Bach, S. Galgani, C. Gasperini, L. Ottoboni, D. Ciabini, M. D. Caramia, G. Bernardi, et al. CD8+ T cells from patients with acute multiple sclerosis display selective increase of adhesiveness in brain venules: a critical role for P-selectin glycoprotein ligand-1 Blood, June 15, 2003; 101(12): 4775 - 4782. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Lagadec, O. Dejoux, M. Ticchioni, F. Cottrez, M. Johansen, E. J. Brown, and A. Bernard Involvement of a CD47-dependent pathway in platelet adhesion on inflamed vascular endothelium under flow Blood, June 15, 2003; 101(12): 4836 - 4843. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Nishijima, J. Kiryu, A. Tsujikawa, M. Honjo, A. Nonaka, K. Yamashiro, H. Kamizuru, Y. Ieki, H. Tanihara, Y. Honda, et al. Inhibitory Effects of Antithrombin III on Interactions between Blood Cells and Endothelial Cells during Retinal Ischemia-Reperfusion Injury Invest. Ophthalmol. Vis. Sci., January 1, 2003; 44(1): 332 - 341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. G. James, D. C. Bullard, and M. J. Hickey Critical Role of the {alpha}4 Integrin/VCAM-1 Pathway in Cerebral Leukocyte Trafficking in Lupus-Prone MRL/faslpr Mice J. Immunol., January 1, 2003; 170(1): 520 - 527. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Andonegui, S. M. Goyert, and P. Kubes Lipopolysaccharide-Induced Leukocyte-Endothelial Cell Interactions: A Role for CD14 Versus Toll-Like Receptor 4 Within Microvessels J. Immunol., August 15, 2002; 169(4): 2111 - 2119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Kerfoot and P. Kubes Overlapping Roles of P-Selectin and {alpha}4 Integrin to Recruit Leukocytes to the Central Nervous System in Experimental Autoimmune Encephalomyelitis J. Immunol., July 15, 2002; 169(2): 1000 - 1006. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Piccio, B. Rossi, E. Scarpini, C. Laudanna, C. Giagulli, A. C. Issekutz, D. Vestweber, E. C. Butcher, and G. Constantin Molecular Mechanisms Involved in Lymphocyte Recruitment in Inflamed Brain Microvessels: Critical Roles for P-Selectin Glycoprotein Ligand-1 and Heterotrimeric Gi-Linked Receptors J. Immunol., February 15, 2002; 168(4): 1940 - 1949. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Lefer Platelets : Unindicted Coconspirators in Inflammatory Tissue Injury Circ. Res., December 8, 2000; 87(12): 1077 - 1078. [Full Text] [PDF]
|
|