Animal platelets

Despite the description of several examples of impaired functional and biochemical responses to TP receptor agonists in human and animal platelets (70-76), only one TP receptor mutation has been described (77). A single amino acid substitution (R -L) was found in hxrman TXR-a cDNA obtained by RT-PCR from platelets of patients with a dominantly inherited bleeding disorder (See V. ALTERED TP RECEPTOR FUNCTION, A. TP RECEPTOR MUTATION below). 

Conpared to human platelets, the fimctional responses of animal platelets to TP receptor agonists are quite varied. Platelets fh)m some species, such as cats, guinea pigs and rabbits, were repotted to aggregate irreversibly when stirred with sodium arachidonate or 9,ll-azo-PGH2, while sheep and dog platelets feiled to aggregate under the same conditions (74,172). Horse platelets aggregated reversibly in response to arachidonate... 

Similar results have been reported in sublethaHy and lethaHy irradiated dogs, where G-CSF reduced the severity and duration of neutropenia and the duration of thrombocytopenia (161). G-CSF increases the survival of lethaHy irradiated animals by inducing eadier recovery of neutrophils and platelets. GM-CSF also decreases the severity and duration of neutropenia in dogs exposed to 2.4 Gy (2400 rad) TBI, but does not influence monocyte or lymphocyte recovery (162), indicating its expected selective action. 

Platelet activating factor (PAF) was first identified by its ability (at low levels) to cause platelet aggregation and dilation of blood vessels, but it is now known to be a potent mediator in inflammation, allergic responses, and shock. PAF effects are observed at tissue concentrations as low as 10 M. PAF causes a dramatic inflammation of air passages and induces asthma-like symptoms in laboratory animals. Toxic-shock syndrome occurs when fragments of destroyed bacteria act as toxins and induce the synthesis of PAF. This results in a drop in blood pressure and a reduced... 

Animal cells can modify arachidonic acid and other polyunsaturated fatty acids, in processes often involving cyclization and oxygenation, to produce so-called local hormones that (1) exert their effects at very low concentrations and (2) usually act near their sites of synthesis. These substances include the prostaglandins (PG) (Figure 25.27) as well as thromboxanes (Tx), leukotrienes, and other hydroxyeicosanoic acids. Thromboxanes, discovered in blood platelets (thrombocytes), are cyclic ethers (TxBg is actually a hemiacetal see Figure 25.27) with a hydroxyl group at C-15. 

In practice, some anticoagulation agents such as heparin or antiplatelet agents, e.g. nitric oxide (NO) are delivered to sensor sites in order to reduce the risk of thrombus formation. Nitric oxide (NO), which is a potent inhibitor of platelet adhesion and activation as well as a promoter of wound healing in tissue, has been incorporated in various polymer metrics including PVC (poly(vinyl-chloride)), PDMS (poly-dimethyl-siloxane) and PU (poly-urethanes). Those NO release polymers have been tested in animals as outer protection coatings and have shown promising effects for the analytical response characteristics of the sensor devices [137],... 

IL-6 participates in both atherogenesis and inflammatory processes. In one interesting mouse model that was double deficient at the apoE and IL-6 loci, animals displayed similar hypercholesterolemia compared to apoE-null mice, but disclosed larger and more calcified lesions at 1 year of age (Klinge 2001). Thus, IL-6 appears to be involved at the fibrous plaque stage of the atherosclerotic process. Moreover, IL-6 is a key factor in the generation of the hepatic acute-phase response and so increases the levels of CRP, fibrinogen, platelet... 

Consumption of fish oil in excess can generate immunotoxic effects in laboratory animals. Rats fed a 17% fish oil diet had reduced wound-healing responses when compared to com oil [59], In a mouse model of bacterial resistance to S. typhimurium, lower survival rates were reported for those animals that ingested a 20% fish oil diet over 15 days [59], Similar fish oil-induced effects in guinea pigs were noted in a study of experimental tuberculosis leading the authors to conclude that this treatment resulted in decreased resistance to infectious disease. The consumption of fish oil has also been reported to result in alterations of hemostatic parameters such as platelet production and function. However, there is no indication that at doses normally consumed by humans, immunotoxicity will occur. 

Administration of Certain Proteases to Animals Enhances Metastasis. Administration of specific proteases to animals has been found to stimulate the production of metastasis. For example, in rabbits, administration of uPA has been found to enhance the metastasis of V2 carcinomas (K11), while in mice, exogenous uPA increased pulmonary metastasis from Lewis lung carcinomas (Tl). Also, infusion of thrombin into syngenic mice stimulated pulmonary metastasis from both colon carcinoma cells and melanoma cells (N5). This enhanced formation of metastasis in the presence of thrombin may result from increased tumor cell-platelet interaction in the presence of the protease (N5). 

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