Differential regulation of CXCR2 trafficking by Rab GTPases

Intracellular trafficking of chemokine receptors plays an important role in fine-tuning the functional responses of neutrophils and lymphocytes in the inflammatory process and HIV infection. Although many chemokine receptors internalize through clathrin-coated pits, regulation of the receptor trafficking is not fully understood. The present study demonstrated that CXCR2 was colocalized with transferrin and low-density lipoprotein (LDL) after agonist treatment for different periods of time, suggesting 2 intracellular trafficking pathways for this receptor. CXCR2 was colocalized with Rab5 and Rab11a, which are localized in early and recycling endosomes, respectively, in response to agonist stimulation for a short period of time, suggesting a recycling pathway for the receptor trafficking. However, overexpression of a dominant-negative Rab5-S34N mutant significantly attenuated CXCR2 sequestration. The internalized CXCR2 was recycled back to the cell surface after removal of the agonist and recovery of the cells, but receptor recycling was inhibited by overexpression of a dominant-negative Rab11a-S25N mutant. After prolonged (4-hour) agonist treatment, CXCR2 exhibited significantly increased colocalization with Rab7, which is localized in late endosomes. The colocalization of CXCR2 with LDL and LAMP-1 suggests that CXCR2 is targeted to lysosomes for degradation after prolonged ligand treatment. However, the colocalization of CXCR2 with Lamp1 was blocked by the overexpression of a dominant-negative Rab7-T22N mutant. In cells overexpressing Rab7-T22N, CXCR2 was retained in the Rab5- and Rab11a-positive endosomes after prolonged (4-hour) agonist treatment. Our data suggest that the intracellular trafficking of CXCR2 is differentially regulated by Rab proteins.     

Effect of storage time on clinical efficacy of single-donor platelet units

Decrements in platelet function and recovery are known to accumulate during the 5-day storage period, and the clinical response to platelets transfused after several days' storage has been suggested by some researchers to be less than that seen with platelets stored for shorter periods. The clinical response to single-donor platelet (SDP) units (as measured by corrected count increments [CCIs] and intertransfusion intervals) was investigated in autologous bone marrow transplant patients. Twenty-seven consecutive autologous bone marrow transplant patients with a variety of hematologic and solid organ malignancies were evaluated for posttransfusion CCIs after 419 SDP transfusions of units stored for 1 to 5 days. Patients were not excluded from the study because of clinical condition, such as fever or sepsis. The mean 15- minute posttransfusion CCI for SDP units stored for only 1 day (11,006 +/− 5,157) was no different than that for units stored for 5 days (10,225 +/− 4,481; p > 0.05); 24-hour posttransfusion CCIs were also not different if the SDP unit had been stored for 1 day or 5 days (6229 +/− 4489 vs. 4786 +/− 2759; p > 0.05) or for any intermediate period. Nor were intertransfusion intervals affected by storage time. While platelets may exhibit a progressive lesion during the 5-day storage period, these changes do not result in a decreased clinical response.     

Enzyme Variability in the Drosophila willistoni Group, I. Genetic Differentiation Among Sibling Species

We have studied by gel electrophoresis the variability of 14 structural genes in four sibling species, Drosophila willistoni, D. paulistorum, D. equinoxialis, and D. tropicalis. Samples of about 30 populations from different parts of the distribution areas of each species were examined. Genetic variants are found at every locus; 67% of the loci are polymorphic, having two or more alleles, the rarer of which has a frequency of 5% or higher.The gene frequencies are fairly uniform over the distribution area of each species, but considerably different in different species. It is estimated that individuals which belong to the different species differ on the average in somewhat more than one half of their gene loci. The morphological similarity of the four sibling species contrasts with the extensive diversity in their genetic materials.