Delayed Mortality and Attenuated Thrombocytopenia Associated with Severe Malaria in Urokinase- and Urokinase Receptor-Deficient Mice

doi:10.1128/IAI.68.7.3822-3829.2000

This Article

	Full Text
	Full Text (PDF)
	Alert me when this article is cited
	Alert me if a correction is posted

Services

	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new issues of the journal
	Download to citation manager
	Reprints and Permissions
	Copyright Information
	Books from ASM Press
	MicrobeWorld

Citing Articles

	Citing Articles via HighWire
	Citing Articles via Google Scholar

Google Scholar

	Articles by Piguet, P. F.
	Articles by Grau, G. E.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Piguet, P. F.
	Articles by Grau, G. E.

Previous Article | Next Article

Infection and Immunity, July 2000, p. 3822-3829, Vol. 68, No. 7
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Delayed Mortality and Attenuated Thrombocytopenia Associated with Severe Malaria in Urokinase- and Urokinase Receptor-Deficient Mice

Pierre Francois Piguet,¹^,^* Chen Da Laperrousaz,¹ Christian Vesin,¹ Fabienne Tacchini-Cottier,² Giorgio Senaldi,³ and Georges Emile Grau⁴

Department of Pathology, University of Geneva, Geneva CH 1211,¹ and Institute of Biochemistry, World Health Organization IRTC, 1066 Epalinges,² Switzerland; Amgen, Inc., Thousand Oaks, California 91320-1789³; and CNRS-UPRES A6020, Université de la Méditerranée, 13385 Marseille, France⁴

Received 8 July 1999/Returned for modification 30 November 1999/Accepted 28 March 2000

We explored the role of urokinase and tissue-type plasminogen activators (uPA and tPA), as well as the uPA receptor (uPAR;CD87) in mouse severe malaria (SM), using genetically deficient( $-$ / $-$ ) mice. The mortality resulting from Plasmodium berghei ANKAinfection was delayed in uPA^/ and uPAR^/ mice but was similar to that of the wild type (+/+) in tPA^/ mice. Parasitemia levels were similar in uPA^/, uPAR^/, and +/+ mice. Production of tumor necrosis factor, as judgedfrom the plasma level and the mRNA levels in brain and lung, wasmarkedly increased by infection in both +/+ and uPAR^/ mice. Breakdown of the blood-brain barrier, as evidenced by theleakage of Evans Blue, was similar in +/+ and uPAR^/ mice. SM was associated with a profound thrombocytopenia, whichwas attenuated in uPA^/ and uPAR^/ mice. Administration of aprotinin, a plasmin antagonist, alsodelayed mortality and attenuated thrombocytopenia. Platelet trappingin cerebral venules or alveolar capillaries was evident in +/+mice but absent in uPAR^/ mice. In contrast, macrophage sequestration in cerebral venulesor alveolar capillaries was evident in both +/+ and uPAR^/ mice. Polymorphonuclear leukocyte sequestration in alveolar capillarieswas similar in +/+ and uPAR^/ mice. These results demonstrate that the uPAR deficiency attenuatesthe severity of SM, probably by its important role in plateletkinetics and trapping. These results therefore suggest that plateletsequestration contributes to the pathogenesis ofSM.

^* Corresponding author. Mailing address: Department of Pathology, 1 rue M. Servet, SMU, 1211 Geneva, Switzerland. Phone: 41-22-70-25-758.Fax: 41-22-70-25-746. E-mail: pierre.piguet{at}medecine.unige.ch.

This article has been cited by other articles:

Raberg, L., Graham, A. L, Read, A. F (2009). Decomposing health: tolerance and resistance to parasites in animals. Phil Trans R Soc B 364: 37-49 [Abstract] [Full Text]
Shushakova, N., Eden, G., Dangers, M., Zwirner, J., Menne, J., Gueler, F., Luft, F. C., Haller, H., Dumler, I. (2005). The Urokinase/Urokinase Receptor System Mediates the IgG Immune Complex-Induced Inflammation in Lung. J. Immunol. 175: 4060-4068 [Abstract] [Full Text]
Penet, M.-F., Viola, A., Confort-Gouny, S., Le Fur, Y., Duhamel, G., Kober, F., Ibarrola, D., Izquierdo, M., Coltel, N., Gharib, B., Grau, G. E., Cozzone, P. J. (2005). Imaging Experimental Cerebral Malaria In Vivo: Significant Role of Ischemic Brain Edema. J. Neurosci. 25: 7352-7358 [Abstract] [Full Text]
Krucken, J., Dkhil, M. A., Braun, J. V., Schroetel, R. M. U., El-Khadragy, M., Carmeliet, P., Mossmann, H., Wunderlich, F. (2005). Testosterone Suppresses Protective Responses of the Liver to Blood-Stage Malaria. Infect. Immun. 73: 436-443 [Abstract] [Full Text]
RAE, C., MCQUILLAN, J. A., PAREKH, S. B., BUBB, W. A., WEISER, S., BALCAR, V. J., HANSEN, A. M., BALL, H. J., HUNT, N. H. (2004). Brain gene expression, metabolism, and bioenergetics: interrelationships in murine models of cerebral and noncerebral malaria. FASEB J. 18: 499-510 [Abstract] [Full Text]
Combes, V., Rosenkranz, A. R., Redard, M., Pizzolato, G., Lepidi, H., Vestweber, D., Mayadas, T. N., Grau, G. E. (2004). Pathogenic Role of P-Selectin in Experimental Cerebral Malaria: Importance of the Endothelial Compartment. Am. J. Pathol. 164: 781-786 [Abstract] [Full Text]
Sun, G., Chang, W.-L., Li, J., Berney, S. M., Kimpel, D., van der Heyde, H. C. (2003). Inhibition of Platelet Adherence to Brain Microvasculature Protects against Severe Plasmodium berghei Malaria. Infect. Immun. 71: 6553-6561 [Abstract] [Full Text]
Nagayasu, E., Nagakura, K., Akaki, M., Tamiya, G., Makino, S., Nakano, Y., Kimura, M., Aikawa, M. (2002). Association of a Determinant on Mouse Chromosome 18 with Experimental Severe Plasmodium berghei Malaria. Infect. Immun. 70: 512-516 [Abstract] [Full Text]
Lou, J., Lucas, R., Grau, G. E. (2001). Pathogenesis of Cerebral Malaria: Recent Experimental Data and Possible Applications for Humans. Clin. Microbiol. Rev. 14: 810-820 [Abstract] [Full Text]
Piguet, P. F., Da Kan, C., Vesin, C., Rochat, A., Donati, Y., Barazzone, C. (2001). Role of CD40-CD40L in Mouse Severe Malaria. Am. J. Pathol. 159: 733-742 [Abstract] [Full Text]