Platelet-Activating Factor Antagonists Decrease Follicular Dendritic-Cell Stimulation of Human B Lymphocytes

Both B-lymphoblastoid cell lines and tonsillar B lymphocytes express receptors for platelet-activating factor (PAF). In lymph node germinal centres, B lymphocytes interact with follicular dendritic cells (FDCs), which present antigen-containing immune complexes to B lymphocytes. FDCs have phenotypic features that are similar to those of stromal cells and monocytes and may therefore be a source of lipid mediators. In this study, we evaluated the effects of the PAF antagonist WEB 2170 on the activation of tonsillar B lymphocytes by FDCs. FDCs were isolated from tonsils by Bovine Serum Albumin (BSA) gradient centrifugation. After being cultured for 6 to 10 days, they were incubated with freshly isolated B cells in the presence or absence of the specific PAF receptor antagonist WEB 2170. B-lymphocyte proliferation was assessed by [3H]-thymidine incorporation, and immunoglobulin (Ig) G and IgM secretion was assessed by enzyme-linked immunosorbent assay (ELISA). WEB 2170 (10-6 to 10-8 M) inhibited [3H]-thymidine incorporation by up to 35% ± 3%. Moreover, the secretion of IgG and IgM was inhibited by up to 50% by WEB 2170 concentrations ranging from 10-6 to 10-8 M. There was no evidence of toxicity by trypan blue staining, and the addition of WEB 2170 to B cells in the absence of FDCs did not inhibit the spontaneous production of IgG or IgM. The effect of the PAF antagonist is primarily on B lymphocytes, as reverse transcription polymerase chain reaction detected little PAF receptor messenger ribonucleic acid (mRNA) from FDCs. These data suggest that endogenous production of PAF may be important in the interaction of B lymphocytes with FDCs

Abstract 494: The Impact of Renal Insufficiency on Carotid Artery Disease Regression in an Academic Medical Center

Introduction: In the United States, 3% of adults are affected by carotid artery disease, and the prevalence is higher in patients with concomitant renal insufficiency. Ischemic events are also more common in patients with renal insufficiency and significantly contribute to morbidity and mortality. Despite the prevalence of carotid artery disease in individuals with renal insufficiency, only a few studies have examined the rate of carotid disease progression in this high risk group, and the mechanisms underlying disease progression are largely unknown. Hypothesis: Patients with any stage of renal insufficiency will have an accelerated rate of carotid artery atherosclerotic progression compared to patients with normal renal function. Methods: Retrospective chart review was performed on 171 consecutive patients referred to Cooper University Hospital for non invasive evaluation of carotid artery disease. Severity of carotid artery disease was evaluated with carotid doppler, and each patient had at least two carotid doppler studies performed at least 6 months apart. The sample was divided into 2 groups - [Group 1] GFR &gt; 60 and [Group 2] GFR &lt;60. Demographics, comorbidities, medications, serum creatinine, MDRD GFR and ultrasound analysis (proximal peak systolic velocity (PSV), and proximal end diastolic velocity (EDV)) were recorded. The average change in the PSV between studies for the 2 groups were calculated and compared. None of the patients in the sample were on dialysis. Results: Preliminary results revealed carotid artery disease regression in both groups; however, patients with any stage of renal insufficiency had less carotid artery disease regression compared to patients with normal renal function. Conclusions: Renal insufficiency negatively impacts the rate of carotid artery disease regression in patients with carotid artery disease. These results suggest that patients with renal insufficiency may require more aggressive follow-up and/or earlier invasive interventions of carotid artery disease. Current monitoring and treatment standards should be improved to adequately address the needs of this high risk subgroup. </jats:p