Urokinase does not upregulate the vascular endothelial cell–mediated inflammatory response

AbstractPurpose: Urokinase is used clinically for thrombolysis, but little is known of its direct effect on vascular endothelial cells. The following experiments were preformed to assess the in vitro effects of urokinase on vascular endothelial cell growth, adhesion molecule expression, and interaction with lymphocytes, polymorphonuclear leukocytes, and platelets.Methods: Commercially available human umbilical vein endothelial cells (HUVEC) were cultured with varying concentrations of urokinase (0 to 10,000 IU/ml) (clinical dosage, ≤500 IU/ml). HUVEC viability was determined from 1 to 4 days. HUVECs were incubated with urokinase (0 to 2000 IU/ml) from 4 to 72 hours. Adherence of 51-chromium-labeled polymorphonuclear leukocytes, platelets, or lymphocytes was then quantitated. In separate experiments HUVEC adhesion molecule expression (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, or endothelial leukocyte adhesion molecule-1) was determined by flow cytometry.Results: There was a decrease of HUVEC viability at suprapharmacologic urokinase concentrations of ≥2000 IU/ml compared with nontreated control samples (0 IU/ml, 73% ± 2%, 2000 IU/ml, 60.5% ± 1.9%, p < 0.05) presumably because of drug toxicity. There was no significantly increased polymorphonuclear leukocyte, lymphocyte, or platelet adhesion to urokinase-treated HUVEC monolayers at any time point. This was also true for each adhesion molecule tested.Conclusions: Urokinase at clinically relevant concentrations (≤500 IU/ml) did not affect endothelial cell viability or growth, nor did it upregulate adhesion molecule expression or cellular adhesion associated with the local vascular inflammatory response. It is therefore implied that the use of urokinase in vivo similarly would not initiate the vascular inflammatory response. (J Vasc Surg 1997;25:471-80.

Ecological selection pressures for C4 photosynthesis in the grasses

Grasses using the C4 photosynthetic pathway dominate grasslands and savannahs of warm regions, and account for half of the species in this ecologically and economically important plant family. The C4 pathway increases the potential for high rates of photosynthesis, particularly at high irradiance, and raises water-use efficiency compared with the C3 type. It is therefore classically viewed as an adaptation to open, arid conditions. Here, we test this adaptive hypothesis using the comparative method, analysing habitat data for 117 genera of grasses, representing 15 C4 lineages. The evidence from our three complementary analyses is consistent with the hypothesis that evolutionary selection for C4 photosynthesis requires open environments, but we find an equal likelihood of C4 evolutionary origins in mesic, arid and saline habitats. However, once the pathway has arisen, evolutionary transitions into arid habitats occur at higher rates in C4 than C3 clades. Extant C4 genera therefore occupy a wider range of drier habitats than their C3 counterparts because the C4 pathway represents a pre-adaptation to arid conditions. Our analyses warn against evolutionary inferences based solely upon the high occurrence of extant C4 species in dry habitats, and provide a novel interpretation of this classic ecological association