|
|
 Previous Article | Table of Contents | Next Article 
Blood, 1 June 2002, Vol. 99, No. 11, pp. 4160-4165
PHAGOCYTES
Neutrophil activation by heme: implications for inflammatory
processes
Aurélio V. Graça-Souza,
Maria Augusta B. Arruda,
Marta
S. de Freitas,
Christina Barja-Fidalgo, and
Pedro L. Oliveira
From the Departamento de Farmacologia, Instituto de
Biologia, Universidade do Estado do Rio de Janeiro; and Departamento de
Bioquimica Médica, Instituto de Ciências Biomédicas,
Centro de Ciências da Saúde, Universidade Federal do Rio de
Janeiro, Brazil.
Heme, a ubiquitous iron-containing compound, is present in large
amounts in many cells and is inherently dangerous, particularly when it
escapes from intracellular sites. The release of heme from damaged
cells and tissues is supposed to be higher in diseases such as malaria
and hemolytic anemia or in trauma and hemorrhage. We investigated here
the role of free ferriprotoporphyrin IX (hemin) as a proinflammatory
molecule, with particular attention to its ability to activate
neutrophil responses. Injecting hemin into the rat pleural cavity
resulted in a dose-dependent migration of neutrophils, indicating that
hemin is able to promote the recruitment of these cells in vivo. In
vitro, hemin induced human neutrophil chemotaxis and cytoskeleton
reorganization, as revealed by the increase of neutrophil actin
polymerization. Exposure of human neutrophils to 3 µM hemin activated
the expression of the chemokine interleukin-8, as demonstrated by
quantitative reverse-transcription polymerase chain reaction,
indicating a putative molecular mechanism by which hemin induces
chemotaxis in vivo. Brief incubation of human neutrophils with
micromolar concentrations of hemin (1-20 µM) triggered the oxidative
burst, and the production of reactive oxygen species was directly
proportional to the concentration of hemin added to the cells. Finally,
we observed that human neutrophil protein kinase C was activated by
hemin in vitro, with a K1/2 of 5 µM. Taken together,
these results suggest a role for hemin as a proinflammatory agent able
to induce polymorphonuclear neutrophil activation in situations of
clinical relevance, such as hemolysis or hemoglobinemia.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
A. L. Lagan, D. D. Melley, T. W. Evans, and G. J. Quinlan
Pathogenesis of the systemic inflammatory syndrome and acute lung injury: role of iron mobilization and decompartmentalization
Am J Physiol Lung Cell Mol Physiol,
February 1, 2008;
294(2):
L161 - L174.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Nuchsongsin, K. Chotivanich, P. Charunwatthana, O.-S. Fausta, D. Taramelli, N. P. Day, N. J. White, and A. M. Dondorp
Effects of Malaria Heme Products on Red Blood Cell Deformability
Am J Trop Med Hyg,
October 1, 2007;
77(4):
617 - 622.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. D. Dimitrov, L. T. Roumenina, V. R. Doltchinkova, N. M. Mihaylova, S. Lacroix-Desmazes, S. V. Kaveri, and T. L. Vassilev
Antibodies Use Heme as a Cofactor to Extend Their Pathogen Elimination Activity and to Acquire New Effector Functions
J. Biol. Chem.,
September 14, 2007;
282(37):
26696 - 26706.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. N. Porto, L. S. Alves, P. L. Fernandez, T. P. Dutra, R. T. Figueiredo, A. V. Graca-Souza, and M. T. Bozza
Heme Induces Neutrophil Migration and Reactive Oxygen Species Generation through Signaling Pathways Characteristic of Chemotactic Receptors
J. Biol. Chem.,
August 17, 2007;
282(33):
24430 - 24436.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. T. Figueiredo, P. L. Fernandez, D. S. Mourao-Sa, B. N. Porto, F. F. Dutra, L. S. Alves, M. F. Oliveira, P. L. Oliveira, A. V. Graca-Souza, and M. T. Bozza
Characterization of Heme as Activator of Toll-like Receptor 4
J. Biol. Chem.,
July 13, 2007;
282(28):
20221 - 20229.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Pierrot, E. Adam, D. Hot, S. Lafitte, M. Capron, J. D. George, and J. Khalife
Contribution of T Cells and Neutrophils in Protection of Young Susceptible Rats from Fatal Experimental Malaria
J. Immunol.,
February 1, 2007;
178(3):
1713 - 1722.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Walther, J. Woodruff, F. Edele, D. Jeffries, J. E. Tongren, E. King, L. Andrews, P. Bejon, S. C. Gilbert, J. B. De Souza, et al.
Innate Immune Responses to Human Malaria: Heterogeneous Cytokine Responses to Blood-Stage Plasmodium falciparum Correlate with Parasitological and Clinical Outcomes
J. Immunol.,
October 15, 2006;
177(8):
5736 - 5745.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. J. Schaer, C. A. Schaer, P. W. Buehler, R. A. Boykins, G. Schoedon, A. I. Alayash, and A. Schaffner
CD163 is the macrophage scavenger receptor for native and chemically modified hemoglobins in the absence of haptoglobin
Blood,
January 1, 2006;
107(1):
373 - 380.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Dey, A. Sarkar, N. Majumder, S. Bhattacharyya (Majumdar), K. Roychoudhury, S. Bhattacharyya, S. Roy, and S. Majumdar
Regulation of Impaired Protein Kinase C Signaling by Chemokines in Murine Macrophages during Visceral Leishmaniasis
Infect. Immun.,
December 1, 2005;
73(12):
8334 - 8344.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Nascimento-Silva, M. A. Arruda, C. Barja-Fidalgo, C. G. Villela, and I. M. Fierro
Novel lipid mediator aspirin-triggered lipoxin A4 induces heme oxygenase-1 in endothelial cells
Am J Physiol Cell Physiol,
September 1, 2005;
289(3):
C557 - C563.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. A. Lara, U. Lins, G. H. Bechara, and P. L. Oliveira
Tracing heme in a living cell: hemoglobin degradation and heme traffic in digest cells of the cattle tick Boophilus microplus
J. Exp. Biol.,
August 15, 2005;
208(16):
3093 - 3101.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. P. Rother, L. Bell, P. Hillmen, and M. T. Gladwin
The Clinical Sequelae of Intravascular Hemolysis and Extracellular Plasma Hemoglobin: A Novel Mechanism of Human Disease
JAMA,
April 6, 2005;
293(13):
1653 - 1662.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Bitzan, B. B. Bickford, and G. H. Foster
Verotoxin (Shiga Toxin) Sensitizes Renal Epithelial Cells to Increased Heme Toxicity: Possible Implications for the Hemolytic Uremic Syndrome
J. Am. Soc. Nephrol.,
September 1, 2004;
15(9):
2334 - 2343.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Arruda, A. G. Rossi, M. S. de Freitas, C. Barja-Fidalgo, and A. V. Graca-Souza
Heme Inhibits Human Neutrophil Apoptosis: Involvement of Phosphoinositide 3-Kinase, MAPK, and NF-{kappa}B
J. Immunol.,
August 1, 2004;
173(3):
2023 - 2030.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Osakabe, A. Yasuda, M. Natsume, and T. Yoshikawa
Rosmarinic acid inhibits epidermal inflammatory responses: anticarcinogenic effect of Perilla frutescens extract in the murine two-stage skin model
Carcinogenesis,
April 1, 2004;
25(4):
549 - 557.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Liu and Z. Spolarics
Methemoglobin is a potent activator of endothelial cells by stimulating IL-6 and IL-8 production and E-selectin membrane expression
Am J Physiol Cell Physiol,
November 1, 2003;
285(5):
C1036 - C1046.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. A. D. T. G. Wagener, H. E. van Beurden, J. W. von den Hoff, G. J. Adema, and C. G. Figdor
The heme-heme oxygenase system: a molecular switch in wound healing
Blood,
July 15, 2003;
102(2):
521 - 528.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
