The adhesion of Plasmodium falciparum-infected erythrocytes (IRBCs) to human dermal microvascular endothelial cells (HDMECs) under flow conditions is regulated by a Src family kinase-and alkaline phosphatase (AP)-dependent mechanism. In this study, we showed that the target of the phosphatase activity is the ectodomain of CD36 at threonine-92 (Thr 92 ). Mouse fibroblasts (NIH 3T3 cells) transfected with wild-type CD36 or a mutant protein in which Thr 92 was substituted by Ala supported the rolling and adhesion of IRBCs. However, while the Src family kinase inhibitors PP1 and PP2 and the specific AP inhibitor levamisole significantly reduced IRBC adhesion to wild-type CD36 transfectants as with HDMECs, the inhibitors had no effect on IRBC adhesion to the mutant cells. Using a phosphospecific antibody directed at a 12-amino-acid peptide spanning Thr 92 , we demonstrated directly that CD36 was constitutively phosphorylated and could be dephosphorylated by exogenous AP. Endothelial CD36 was likewise constitutively phosphorylated. The phosphospecific antibody inhibited IRBC adhesion to HDMECs that could be reversed by preincubating the antibody with the phosphorylated but not the nonphosphorylated peptide. Pretreatment of HDMECs with AP abrogated the effect of PP1 on IRBC adhesion. Collectively, these results are consistent with a critical role for CD36 dephosphorylation through Src family kinase activation in regulating IRBC adhesion to vascular endothelium.The scavenger receptor CD36 expressed on erythroblasts, platelets, monocytes/macrophages, dendritic cells, microvascular endothelial cells, striated muscle cells, adipocytes, and mammary epithelial cells is increasingly recognized as a signaling molecule and/or coreceptor for diverse ligands that are implicated in the pathogenesis of major inflammatory diseases. Specifically, CD36 has been shown to elicit a proinflammatory response in microglial cells in the brain (3, 22) and macrophages in an atheroma (21) through its interaction with fibrillar ␤-amyloid. In binding to CD36, ␤-amyloid inhibits CD36-mediated clearance of oxidized lipoproteins and thus promotes accumulation of lipid peroxidases and accelerated atherogenesis (19). Evidence is also emerging that CD36 acts as a coreceptor for some but not all bacterial ligands for Toll-like receptor 2 activation (17). As a result, CD36-deficient mice were hypersusceptible to the gram-positive microbe Staphylococcus aureus.In Plasmodium falciparum malaria, CD36 has long been considered a major contributor to pathogenesis by acting as a vascular receptor for the adhesion of infected erythrocytes (IRBCs) (16). The deleterious effect of cytoadherence has been attributed to impairment of microcirculatory blood flow, with subsequent tissue hypoxia and organ dysfunction. There is strong clinical evidence to support this mechanical mechanism, such as the demonstration of lower-than-expected oxygen tension and reduced perfusion pressure in the cerebral circulation of patients with cerebral malaria (23,28). IRBC adhesion may a...

In 1983, the Clearwater National Forest and the Bonneville Power Administration (BPA) entered into a contractual agreement to improve anadromous fish habitat in selected tributaries of the Cleat-water River Basin. This agreement was drawn under the auspices of the Northwest Power Act of 1980 and the Columbia River Basin Fish and Wildlife Program (section 700). The Program was completed in 1990 and this document constitutes the 'Final Report' that details all project activities, costs, accomplishments, and responses. The Program was funded by BPA with a budget of $425,679 and consisted of 13 projects with 93% of the funding applied 70 the ground'. During this period, the Forest Service contributed a total of $255,000 additional dollars to the Program on a cost-share basis. The overall goal of the Program was to enhance spawning, rearing, and riparian habitats of Lolo Creek and major tributaries of the Lochsa River so that their production systems could reach full capability and help speed the recovery of salmon and steelhead within the basin. In Lofo Creek, we modified six major barriers to upstream passage and accessed a total of 70.0 km of mainstem and tributary habitats for salmon and steelhead. In the Lochsa, we treated 22 major barriers, and provided 118.2 km of mainstem and tributary habitats for anadromous fish. In terms of enhancement, 250,000m2 of rearing habitat and 34.4 ha of riparian habitat were improved in the Lolo Creek system. For the tributaries of the Lochsa, we improved 277,OOOnV of rearing and 6,500m2 of spawning habitats for salmon and steelhead. Overall, our objective attainment level for the Program averaged 205%. We were able to exceed our objective levels because of the relatively low unit costs. The state of Idaho evaluated some of the projects of this Program. They concluded that barrier removals or modiiications have had the greatest (potential) benefit in terms of parr produced. The Clearwater Forest evaluated other instream improvement projects within the Lochsa River system and statistically detected significantly higher parr densities of steelhead in enhanced over control sites in Pete King, Squaw, Papoose, and East Fork Papoose Creeks over a period of 3-5 years. A similar response for chinook parr was observed in Squaw Creek. Differences in salmonid parr densities were observed in summer and winter rearing habitats in Squaw and Papoose Creeks. We believe that habitat enhancement is one of many management tools that is important to the rearing of wild and natural stocks of salmon and steelhead in Idaho. It could make the difference between extinction and marginal existence in some local populations.

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