Thrombin functions as an inflammatory mediator through activation of its receptor

doi:10.1084/jem.183.3.821

This Article

	Full Text (PDF)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Cirino, G.
	Articles by Stone, S. R.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Cirino, G.
	Articles by Stone, S. R.


Social Bookmarking

	What's this?

ARTICLES

Thrombin functions as an inflammatory mediator through activation of its receptor

G Cirino, C Cicala, MR Bucci, L Sorrentino, JM Maraganore and SR Stone
Dipartimento di Farmacologia Sperimentale, Universita degli Studi di Napoli Federico II, Naples, Italy.

A rat model of inflammation was used to investigate the biological effects of thrombin. The thrombin-specific inhibitor Hirulog markedly attentuated the carrageenin-induced edema of the paw of the rat. Injection of thrombin into the paw also produced edema. The effect of thrombin was due to activation of its receptor; a thrombin receptor activating peptide (TRAP) reproduced the effects of thrombin in causing edema. TRAP also increased vascular permeability as demonstrated by extravasation of Evans blue and 125I-labeled serum albumin. The release of bioactive amines played an important role in mediating the TRAP- induced edema; the serotonin/histamine antagonist cryproheptadine and the histamine H2 receptor antagonist cimetidine reduced significantly the edema caused by TRAP. Treatment of rats with the mast cell degranulator 48/80 to deplete these cells of their stores of histamine and serotonin abolished completely the ability of TRAP to produce edema. Histochemical examination confirmed that TRAP treatment led to mast cell degranulation. Thus, it has been possible to demonstrate that thrombin acts as an inflammatory mediator in vivo by activating its receptor, which in turn leads to release of vasoactive amines from mast cells.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Bastarache, J. A., Wang, L., Wang, Z., Albertine, K. H., Matthay, M. A., Ware, L. B. (2008). Intra-alveolar tissue factor pathway inhibitor is not sufficient to block tissue factor procoagulant activity. Am. J. Physiol. Lung Cell. Mol. Physiol. 294: L874-L881 [Abstract] [Full Text]
Peckham, R. M., Handrigan, M. T., Bentley, T. B., Falabella, M. J, Chrovian, A. D., Stahl, G. L., Tsokos, G. C. (2007). C5-blocking antibody reduces fluid requirements and improves responsiveness to fluid infusion in hemorrhagic shock managed with hypotensive resuscitation. J. Appl. Physiol. 102: 673-680 [Abstract] [Full Text]
Camerer, E., Cornelissen, I., Kataoka, H., Duong, D. N., Zheng, Y.-W., Coughlin, S. R. (2006). Roles of protease-activated receptors in a mouse model of endotoxemia. Blood 107: 3912-3921 [Abstract] [Full Text]
Farivar, A. S., Delgado, M. F., McCourtie, A. S., Barnes, A. D., Verrier, E. D., Mulligan, M. S. (2006). Crosstalk Between Thrombosis and Inflammation in Lung Reperfusion Injury.. Ann. Thorac. Surg. 81: 1061-1067 [Abstract] [Full Text]
Howell, D. C.J., Johns, R. H., Lasky, J. A., Shan, B., Scotton, C. J., Laurent, G. J., Chambers, R. C. (2005). Absence of Proteinase-Activated Receptor-1 Signaling Affords Protection from Bleomycin-Induced Lung Inflammation and Fibrosis. Am. J. Pathol. 166: 1353-1365 [Abstract] [Full Text]
Song, S. J., Pagel, C. N., Campbell, T. M., Pike, R. N., Mackie, E. J. (2005). The Role of Protease-Activated Receptor-1 in Bone Healing. Am. J. Pathol. 166: 857-868 [Abstract] [Full Text]
Buresi, M. C., Vergnolle, N., Sharkey, K. A., Keenan, C. M., Andrade-Gordon, P., Cirino, G., Cirillo, D., Hollenberg, M. D., MacNaughton, W. K. (2005). Activation of proteinase-activated receptor-1 inhibits neurally evoked chloride secretion in the mouse colon in vitro. Am. J. Physiol. Gastrointest. Liver Physiol. 288: G337-G345 [Abstract] [Full Text]
Hemdahl, A.-L., Falk, E., Thoren, P., Hansson, G. K. (2004). Thrombin inhibitor reduces myocardial infarction in apoE-/- x LDLR-/- mice. Am. J. Physiol. Heart Circ. Physiol. 287: H872-H877 [Abstract] [Full Text]
Curry, F. E., Zeng, M., Adamson, R. H. (2003). Thrombin increases permeability only in venules exposed to inflammatory conditions. Am. J. Physiol. Heart Circ. Physiol. 285: H2446-H2453 [Abstract] [Full Text]
Sprong, T., Brandtzaeg, P., Fung, M., Pharo, A. M., Hoiby, E. A., Michaelsen, T. E., Aase, A., van der Meer, J. W. M., van Deuren, M., Mollnes, T. E. (2003). Inhibition of C5a-induced inflammation with preserved C5b-9-mediated bactericidal activity in a human whole blood model of meningococcal sepsis. Blood 102: 3702-3710 [Abstract] [Full Text]
Kataoka, H., Hamilton, J. R., McKemy, D. D., Camerer, E., Zheng, Y.-W., Cheng, A., Griffin, C., Coughlin, S. R. (2003). Protease-activated receptors 1 and 4 mediate thrombin signaling in endothelial cells. Blood 102: 3224-3231 [Abstract] [Full Text]
Colognato, R., Slupsky, J. R., Jendrach, M., Burysek, L., Syrovets, T., Simmet, T. (2003). Differential expression and regulation of protease-activated receptors in human peripheral monocytes and monocyte-derived antigen-presenting cells. Blood 102: 2645-2652 [Abstract] [Full Text]
Klarenbach, S. W., Chipiuk, A., Nelson, R. C., Hollenberg, M. D., Murray, A. G. (2003). Differential Actions of PAR2 and PAR1 in Stimulating Human Endothelial Cell Exocytosis and Permeability: The Role of Rho-GTPases. Circ. Res. 92: 272-278 [Abstract] [Full Text]
Lang, R., Song, P. I., Legat, F. J., Lavker, R. M., Harten, B., Kalden, H., Grady, E. F., Bunnett, N. W., Armstrong, C. A., Ansel, J. C. (2003). Human Corneal Epithelial Cells Express Functional PAR-1 and PAR-2. IOVS 44: 99-105 [Abstract] [Full Text]
Sanchez-Pernaute, O., Lopez-Armada, M. J., Calvo, E., Diez-Ortego, I., Largo, R., Egido, J., Herrero-Beaumont, G. (2003). Fibrin generated in the synovial fluid activates intimal cells from their apical surface: a sequential morphological study in antigen-induced arthritis. Rheumatology (Oxford) 42: 19-25 [Abstract] [Full Text]
Kinoshita, M., Miyamoto, T., Ohashi, N., Sasayama, S., Matsumori, A. (2002). Thrombosis Increases Circulatory Hepatocyte Growth Factor by Degranulation of Mast Cells. Circulation 106: 3133-3138 [Abstract] [Full Text]
BURESI, M. C., BURET, A. G., HOLLENBERG, M. D., MacNAUGHTON, W. K. (2002). Activation of proteinase-activated receptor 1 stimulates epithelial chloride secretion through a unique MAP kinase- and cyclo-oxygenase-dependent pathway. FASEB J. 16: 1515-1525 [Abstract] [Full Text]
Mollnes, T. E., Brekke, O.-L., Fung, M., Fure, H., Christiansen, D., Bergseth, G., Videm, V., Lappegard, K. T., Kohl, J., Lambris, J. D. (2002). Essential role of the C5a receptor in E coli-induced oxidative burst and phagocytosis revealed by a novel lepirudin-based human whole blood model of inflammation. Blood 100: 1869-1877 [Abstract] [Full Text]
Szaba, F. M., Smiley, S. T. (2002). Roles for thrombin and fibrin(ogen) in cytokine/chemokine production and macrophage adhesion in vivo. Blood 99: 1053-1059 [Abstract] [Full Text]
Marin, V., Montero-Julian, F. A., Gres, S., Boulay, V., Bongrand, P., Farnarier, C., Kaplanski, G. (2001). The IL-6-Soluble IL-6R{alpha} Autocrine Loop of Endothelial Activation as an Intermediate Between Acute and Chronic Inflammation: an Experimental Model Involving Thrombin. J. Immunol. 167: 3435-3442 [Abstract] [Full Text]
Faivre, S., Regnauld, K., Bruyneel, E., Nguyen, Q.-D., Mareel, M., Emami, S., Gespach, C. (2001). Suppression of Cellular Invasion by Activated G-Protein Subunits Galpha o, Galpha i1, Galpha i2, and Galpha i3 and Sequestration of Gbeta gamma. Mol. Pharmacol. 60: 363-372 [Abstract] [Full Text]
Marin, V., Farnarier, C., Gres, S., Kaplanski, S., Su, M. S.-S., Dinarello, C. A., Kaplanski, G. (2001). The p38 mitogen-activated protein kinase pathway plays a critical role in thrombin-induced endothelial chemokine production and leukocyte recruitment. Blood 98: 667-673 [Abstract] [Full Text]
Bhattacharya, A., Smith, G. F., Cohen, M. L. (2001). Effect of LY287045, a Thrombin/Trypsin Inhibitor, on Thrombin and Trypsin-Induced Aortic Contraction and Relaxation. J. Pharmacol. Exp. Ther. 297: 573-581 [Abstract] [Full Text]
Varisco, P. A., Péclat, V., van Ness, K., Bischof-Delaloye, A., So, A., Busso, N. (2000). Effect of thrombin inhibition on synovial inflammation in antigen induced arthritis. Ann Rheum Dis 59: 781-787 [Abstract] [Full Text]
Shin, H., Kitajima, I., Nakajima, T., Shao, Q., Tokioka, T., Takasaki, I., Hanyu, N., Kubo, T., Maruyama, I. (1999). Thrombin receptor mediated signals induce expressions of interleukin 6 and granulocyte colony stimulating factor via NF-kappa B activation in synovial fibroblasts. Ann Rheum Dis 58: 55-60 [Abstract] [Full Text]
Kaplanski, G., Marin, V., Fabrigoule, M., Boulay, V., Benoliel, A.-M., Bongrand, P., Kaplanski, S., Farnarier, C. (1998). Thrombin-Activated Human Endothelial Cells Support Monocyte Adhesion In Vitro Following Expression of Intercellular Adhesion Molecule-1 (ICAM-1; CD54) and Vascular Cell Adhesion Molecule-1 (VCAM-1; CD106). Blood 92: 1259-1267 [Abstract] [Full Text]
Dery, O., Corvera, C. U., Steinhoff, M., Bunnett, N. W. (1998). Proteinase-activated receptors: novel mechanisms of signaling by serine proteases. Am. J. Physiol. Cell Physiol. 274: C1429-C1452 [Abstract] [Full Text]
Smiley, S. T., Boyer, S. N., Heeb, M. J., Griffin, J. H., Grusby, M. J. (1997). Protein S is inducible by interleukin 4�in T cells and inhibits lymphoid cell procoagulant�activity. Proc. Natl. Acad. Sci. USA 94: 11484-11489 [Abstract] [Full Text]
Chambers, R. C., Leoni, P., Blanc-Brude, O. P., Wembridge, D. E., Laurent, G. J. (2000). Thrombin Is a Potent Inducer of Connective Tissue Growth Factor Production via Proteolytic Activation of Protease-activated Receptor-1. J. Biol. Chem. 275: 35584-35591 [Abstract] [Full Text]