Increased macromolecular leakage through widened gaps between contracted endothelial cells of postcapillary venules is an important event in inflammation. It is induced by a direct action on the venular endothelium of mediators released from mast cells or from activated leukocytes. Cellmediated (polymorphonuclear leukocyte) macromolecular leakage, like that caused by leukotriene B4 is reversible and can be reproduced at 30-minute intervals but that induced by I/R-, PAF-, or parasite-application may cause a state of preconditioning. The HCP is a practicable model for studies on the very first events of inflammation as indicated by the increased rolling/adhesion of leukocytes and macromolecu-lar leakage in postcapillary venules for several reasons: (1) the effects of inflammatory mediators and anti-inflammatory drugs in the HCP have been confirmed in other animal models; (2) measurement of rolling/adhesion of leukocytes and macromolecular leakage can be made simultaneously; and (3) monitored superfusion of the HCP facilitates mediator administration and drug treatment with great accuracy.


Granger, D. N., and Kubes, P. (1994). The microcirculation and inflammation: Modulation of leukocyte-endothelial cell adhesion. J. Leukocyte Biol. 55, 662-675. A comprehensive description and guide for the understanding of leukocyte-endothelial interactions that is still useful although it was published in 1994. Korthuis, R. J., Dayton, C., and Yamaguchi, T. (2003). Early and late preconditioning prevents ischemia/reperfusion injury: Signaling pathways mediating the adaptive metamorphosis to a protective phenotype in preconditioned tissues. In Molecular Basis for Microcirculatory Disorders (G. W. Schmid-Schonbein and D. N. Granger, eds.), pp. 343-363. France, Paris: Springer-Verlag. This review is very useful for the understanding of the phenomenon of preconditioning, an important protective mechanism in inflammation. Ley, K., and Sperandio, M. (2003). Molecular mechanisms of leukocyte adhesion. In Molecular Basis for Microcirculatory Disorders (G. W. Schmid-Schonbein and D. N. Granger, eds.), pp. 1-71. France, Paris:

Springer-Verlag. A very complete review covering all aspects of leukocyte rolling, firm adhesion, and transmigration, and also details of mechanisms of adhesive proteins with references to more than 400 publications.

McDonald, D. M., Thurston, G., and Baluk, P. (1999). Endothelial gaps as sites for plasma leakage in inflammation. Microcirculation 6, 7-22. Persson, C. G. A., and Svensjo, E. (1985). Vascular responses and their suppression: Drugs interfering with venular permeability. In Handbook of Inflammation (I. L. Bonta, M. A. Bray, and M. J. Parnham, eds.), Vol. 5, The Pharmacology of Inflammation, pp. 61-82. Amsterdam, Netherlands: Elsevier. Describes the basis for the concept of the endothelial cells in the postcapillary venules as the site for physiological and pharmacological regulation of vascular permeability increase in inflammation.

Capsule Biography

Dr. Svensjo has worked as senior pharmacologist at two major pharmaceutical companies in Sweden and is now at Laboratorio Imunologia Molecular, Instituto BiofĂ­sica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro. The laboratory focuses on mechanisms of parasite infection (Trypanosoma cruzi, leishmaniasis). The lab is supported by grants from FAPERJ, CNPq, and WHO.

Section D

Permeability, Tone and Hemodynamics

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