![]() |
|
|
Vol. 285, Issue 1, 252-261, April 1998
Center for Experimental Therapeutics and Reperfusion Injury,
Department of Anesthesia, Brigham and Women's Hospital and Harvard
Medical School, Boston, Massachusetts
Neutrophil (PMN) activation and recruitment are coordinated by
ligand-operated surface receptors. These responses are involved in the
tissue injury that follows hypoxia/reoxygenation. Here, we report that
inflammatory mediators each evoke distinct and characteristic
extracellular acidification rates (EAR) in both PMN and endothelial
cells (EC) as measured by a Cytosensor microphysiometer. Leukotriene
B4 (LTB4) and the peptide
N-formylmethionyl-leucyl-phenylalanine were the most potent activators
of EAR, whereas other potent stimuli including interleukin-8 and
platelet-activating factor only weakly stimulated EAR in PMN. In
contrast, other lipid-derived PMN mediators such as prostaglandin
E2 and lipoxin A4 (LXA4) did not
evoke EAR. Ligand-operated EAR exhibited desensitization as well as
ligand specificity and sensitivity to pertussis toxin. Human
endothelial cell agonists including histamine, prostacyclin stable
analog and LXA4 each gave sharply different EAR responses,
with only histamine evoking an EAR in these cells.
Hypoxia/reoxygenation did not alter ligand-operated EAR from PMN, and
similarly LTB4-stimulated PMN transendothelial migration, a
functional response, was not influenced by either PMN or EC exposure to
intervals of hypoxia/reoxygenation. LXA4 stable analogs
inhibited PMN transendothelial migration (1 nM-1 µM), and this
PMN-EC responsiveness to inhibition by a lipoxin stable analog
(e.g., 16-phenoxy-LXA4) was enhanced ~2
log orders of magnitude after hypoxia/reoxygenation. Results
demonstrate that ligand-receptor interactions evoke characteristic
profiles of EAR and that some well-characterized ligand-receptor pairs (including interleukin-8, platelet-activating factor, prostaglandin E2 or LXA4) on these cell types either weakly
activate the EAR pathway or are silent. Furthermore,
hypoxia/reoxygenation did not alter LTB4 PMN responses but
did heighten responsiveness to 16-phenoxy-LXA4, which
suggests a potential protective role in leukocyte-mediated injury.
This article has been cited by other articles:
![]() |
T. Okuno, Y. Iizuka, H. Okazaki, T. Yokomizo, R. Taguchi, and T. Shimizu 12(S)-hydroxyheptadeca-5Z, 8E, 10E-trienoic acid is a natural ligand for leukotriene B4 receptor 2 J. Exp. Med., April 14, 2008; 205(4): 759 - 766. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Arita, F. Bianchini, J. Aliberti, A. Sher, N. Chiang, S. Hong, R. Yang, N. A. Petasis, and C. N. Serhan Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1 J. Exp. Med., March 7, 2005; 201(5): 713 - 722. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Hong, K. Gronert, P. R. Devchand, R.-L. Moussignac, and C. N. Serhan Novel Docosatrienes and 17S-Resolvins Generated from Docosahexaenoic Acid in Murine Brain, Human Blood, and Glial Cells. AUTACOIDS IN ANTI-INFLAMMATION J. Biol. Chem., April 18, 2003; 278(17): 14677 - 14687. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Bonnans, B. Mainprice, P. Chanez, J. Bousquet, and V. Urbach Lipoxin A4 Stimulates a Cytosolic Ca2+ Increase in Human Bronchial Epithelium J. Biol. Chem., March 21, 2003; 278(13): 10879 - 10884. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. M. Fierro, S. P. Colgan, G. Bernasconi, N. A. Petasis, C. B. Clish, M. Arita, and C. N. Serhan Lipoxin A4 and Aspirin-Triggered 15-epi-Lipoxin A4 Inhibit Human Neutrophil Migration: Comparisons Between Synthetic 15 Epimers in Chemotaxis and Transmigration with Microvessel Endothelial Cells and Epithelial Cells J. Immunol., March 1, 2003; 170(5): 2688 - 2694. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. O. Leonard, K. Hannan, M. J. Burne, D. W. P. Lappin, P. Doran, P. Coleman, C. Stenson, C. T. Taylor, F. Daniels, C. Godson, et al. 15-Epi-16-(Para-Fluorophenoxy)-Lipoxin A4-Methyl Ester, a Synthetic Analogue of 15-epi-Lipoxin A4, Is Protective in Experimental Ischemic Acute Renal Failure J. Am. Soc. Nephrol., June 1, 2002; 13(6): 1657 - 1662. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Sorensson, M. Ohlson, A. Bjornson, and B. Haraldsson Orosomucoid has a cAMP-dependent effect on human endothelial cells and inhibits the action of histamine Am J Physiol Heart Circ Physiol, May 1, 2000; 278(5): H1725 - H1731. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Chiang, I. M. Fierro, K. Gronert, and C. N. Serhan Activation of Lipoxin A4 Receptors by Aspirin-triggered Lipoxins and Select Peptides Evokes Ligand-specific Responses in Inflammation J. Exp. Med., April 3, 2000; 191(7): 1197 - 1208. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Hachicha, M. Pouliot, N. A. Petasis, and C. N. Serhan Lipoxin (LX)A4 and Aspirin-triggered 15-epi-LXA4 Inhibit Tumor Necrosis Factor 1alpha -initiated Neutrophil Responses and Trafficking: Regulators of a Cytokine-Chemokine Axis J. Exp. Med., June 21, 1999; 189(12): 1923 - 1930. [Abstract] [Full Text] [PDF] |
||||