"Cross Talk" Plays Role in Tissue Swelling at Acute Inflammation Sites

September 6, 2000

University Park, Pa. --- "Cross talk" between pairs of the smallest blood vessels plays a role in producing tissue swelling at acute inflammation sites, Penn State bioengineers have shown.

Dr. Norman Harris, assistant professor of bioengineering and director of the project, says, "Our novel finding is that communication between pairs of venules and arterioles facilitates signaling to capillaries to release the fluid which causes swelling into the tissues. The idea opens up new routes of investigation for possible interventions to deal with undesirable swelling associated with inflammation."

The Penn State bioengineers detailed their results in a paper, "Requirement of Arteriovenular Pairing for Increased Capillary Filtration during Acute Inflammation," in the current issue of the journal, Microcirculation. The authors are Jason Barnidge, who recently earned his master’s degree in bioengineering at Penn State, and Harris.

Harris explains that current theory holds that, during acute inflammation, white blood cells adhere to the interior walls of venules, the smallest branches of the vein system. These white blood cells cause the venule walls to become more permeable and allow protein to leak into the surrounding tissue.

White blood cells are also thought to cause the capillaries, which branch from the smallest arteries, the arterioles, to become more permeable and leak fluid. However, white blood cells don’t adhere in capillaries and therefore a link is required between the venular site of adherence and the capillaries. A path by which white blood cells in the venules can trigger permeability in the capillaries remained unknown until Harris and co-workers conducted their recent experiments.

The Penn State team used intravital microscopy to observe the microcirculation in living rat tissue. They isolated tissues in which they could observe a venule parallel to and in close pairing with an arteriole that had a branching capillary; an unpaired arteriole with a branching capillary; and an unpaired venule into which a capillary converged. They then treated each of the tissue types with a chemical, FMLP, that stimulates the inflammation response. Only in the tissue in which a venule was in close pairing with an arteriole did the fluid release in the branching capillary increase. Subsequent experiments, in which the micropressure in the capillary was measured, showed that increased fluid release was the result of an increase in permeability.

By observing and counting the movements of the white blood cells, the researchers also were able to make a correlation between the number of white cells near the venule/arteriole pairing site and the increase in fluid release in the capillaries. Harris suggests that the white blood cells may exit the venule through gaps in the blood vessel wall, then migrate closer to the arteriole where they initiate a chemical or electrical signal that is transported by the arteriole to the branching capillaries. The "walk" taken by the white blood cell through the venule wall to the vicinity of the arteriole enables the "cross talk" necessary to signal the capillaries.

The Penn State engineer says that the next step in the research program will be to develop the physical and mathematical theory that can accurately describe the relationship between the arteriole/venule pairing and capillary permeability in order to allow a much more complete characterization of the inflammatory response in a variety of situations.

"Once this goal has been accomplished, it will facilitate testing of hypothetical mechanisms of acute inflammation. Such modeling by biomedical engineers has proved itself invaluable in the past with regard to understanding blood and oxygen delivery to tissue, microvascular permeability to fluid and solute, shear stresses in the microcirculation, segmental resistance and capacitance and many other critical issues," he adds.

The research was supported by a grant from the National Institutes of Health. The Whitaker Foundation also recently awarded Harris a Biomedical Engineering Research grant to continue his studies.

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Contacts:

Barbara Hale (814) 865-9481 (o)/ (814) 238-0997 (h)

Vicki Fong (814) 865-9481 (o)/ (814) 238-1221 (h)

EDITOR: Dr. Harris is at (814) 865-1407 or by email.