Abstract
Background
Polymorphonuclear leukocytes (PMNs) must traverse endogenous chemotactic gradients
(interleukin 8 [IL-8]) before reaching target chemoattractants (fMLP [N-formylmethionine-leucine-phenylalanine],
C5a) produced at a site of bacterial infection. Complement receptor 3 (CR3; CD11b/CD18)
contains 2 distinct binding sites, one that mediates adhesion and a lectin-like domain
(LLD) that binds polysaccharides of microbial origin. This laboratory previously reported
an increase in the chemotactic capacity of PMNs toward fMLP upon ligation of the CR3
LLD with β-glucan, a CR3 agonist. Current studies sought to determine the effect of
β-glucan on PMN navigation toward other chemoattractants alone and in a competing
chemotactic environment.
Methods
Migration was assessed by serum agarose overlay with the use of chambered slides containing
or not, β-glucan. Migration of human PMNs at 37°C for 2 hours was evaluated toward
C5a or IL-8 alone and in competing gradients. Selected groups were treated with anti-CR3–blocking
antibodies. The number of chemotactic cells was quantified by microscopy.
Results
β-glucan significantly enhanced chemotaxis toward C5a and suppressed that toward IL-8
in a CR3-dependent fashion. In the competing chemotactic gradient assays (C5a vs IL-8),
β-glucan further enhanced migration toward C5a while not affecting that toward IL-8.
Conclusions
β-glucan selectively upregulates PMN chemotaxis toward C5a while suppressing chemotaxis
toward IL-8.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to SurgeryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Chemokines.in: John I. Gallin R.S. Inflammation: Basic Principles and Clinical Correlates. Lippincott Williams and Wilkins, Philadelphia1999: 419-431
- An intracellular signaling hierarchy determines direction of migration in opposing chemotactic gradients.J Cell Biol. 2002; 159: 91-102
- Multistep navigation and the combinatorial control of leukocyte chemotaxis.J Cell Biol. 1997; 139: 1349-1360
- Integrins: versatility, modulation, and signaling in cell adhesion.Cell. 1992; 69: 11-25
- Membrane complement receptors specific for bound fragments of C3.Adv Immunol. 1985; 37: 217-267
- Urokinase receptor (CD87) regulates leukocyte recruitment via beta 2 integrins in vivo.J Exp Med. 1998; 188: 1029-1037
- Membrane complement receptor type three (CR3) has lectin-like properties analogous to bovine conglutinin as functions as a receptor for zymosan and rabbit erythrocytes as well as a receptor for iC3b.J Immunol. 1985; 134: 3307-3315
- Generation of recombinant fragments of CD11b expressing the functional beta-glucan-binding lectin site of CR3 (CD11b/CD18).J Immunol. 1999; 162: 7285-7293
- Fungal beta-glucans and mammalian immunity.Immunity. 2003; 19: 311-315
- Promotion of neutrophil chemotaxis through differential regulation of beta 1 and beta 2 integrins.J Immunol. 1999; 162: 6792-6799
- Leukocyte adhesion deficiency syndromes: adhesion and tethering defects involving beta 2 integrins and selectin ligands.Curr Opin Hematol. 2002; 9: 30-35
- ß-Glucan functions as an adjuvant for monoclonal antibody immunotherapy by recruiting tumoricidal granulocytes as killer cells.Cancer Research. 2003; 63: 9023-9031
- Physical association of Gi2alpha with interleukin-8 receptors.J Biol Chem. 1996; 271: 12783-12789
- Role of p38 mitogen-activated protein kinase in chemokine-induced emigration and chemotaxis in vivo.J Immunol. 2001; 167: 6552-6558
- Diverging signal transduction pathways activated by interleukin 8 (IL-8) and related chemokines in human neutrophils. IL-8 and Gro-alpha differentially stimulate calcium influx through IL-8 receptors A and B.J Biol Chem. 1996; 271: 20540-20544
- A novel carbohydrate-glycosphingolipid interaction between a beta-(1-3)-glucan immunomodulator, PGG-glucan, and lactosylceramide of human leukocytes.J Biol Chem. 1998; 273: 22014-22020
- Dectin-1 and its role in the recognition of beta-glucans by macrophages.Mol Immunol. 2004; 40: 869-876
- Randomized phase I/II trial of a macrophage-specific immunomodulator (PGG-glucan) in high-risk surgical patients.Ann Surg. 1994; 220: 601-609
Article info
Publication history
Providence, RI
Footnotes
☆Presented at the 65th Annual Meeting of the Society of University Surgeons, St. Louis, Missouri, February 11-14, 2004.
☆Supported by grants from the National Institutes of Health GM-066194 (J.S.R.) and GM-42859 (J.E.A.), by the Carter Family Charitable Trust (Armand D. Versaci Research Scholar in Surgical Sciences Award to V.L.T.), and by allocations to the Department of Surgery by the Rhode Island Hospital.
Identification
Copyright
© 2004 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
