Modeling FMLP-induced capillary filtration, potential role of oxidatively activated leukocytes

摘要

Microvascular arterioles and venules are typically found in a closely paired countercurrent arrangement that allows diffusional communication. Increases in capillary fluid filtration rate due to acute inflammation appear to utilize this structural arrangement, and are dependent on leukocytes accumulating at arteriovenular pairing sites (Microcirculation 7:259-268, 2000). We have preliminary evidence that following exposure of the rat mesentery to the leukcoyte chemoattractant formyl-met-leu-phe (FMLP), leukocytes that extravasate from postcapillary venules release a signal that is delivered by nearby arterioles to downstream branching capillaries. We hypothesize that such a mechanism can be described in a mathematical model that relates the diffusion distance from a tissue leukocyte to the nearest arteriole, and also the transit time in the bloodstream from the arteriole to capillary. We also hypothesize that leukocytes that are oxidatively activated are the most likely to participate in this mechanism. Following localized FMLP exposure at arteriovenular pairing sites, ～30-50% of tissue leukocytes were oxidativley activated, as defined by cellular fluorescence of the oxidant-senstive dye dihydrorhodamine 123. However, when we measured diffusion distances from those cells to the nearby arteriole, we found no correlation between the estimated effect on capillary filtration (using our mathematical model) and the actual measured effect.