RESUMO
CCL19 and CCL21 are chemokines involved in the trafficking of immune cells, particularly within the lymphatic system, through activation of CCR7. Concurrent expression of PSGL-1 and CCR7 in naive T-cells enhances recruitment of these cells to secondary lymphoid organs by CCL19 and CCL21. Here the solution structure of CCL19 is reported. It contains a canonical chemokine domain. Chemical shift mapping shows the N-termini of PSGL-1 and CCR7 have overlapping binding sites for CCL19 and binding is competitive. Implications for the mechanism of PSGL-1's enhancement of resting T-cell recruitment are discussed.
Assuntos
Quimiocina CCL19/química , Quimiocina CCL19/metabolismo , Glicoproteínas de Membrana/metabolismo , Receptores CCR7/metabolismo , Sítios de Ligação , Humanos , Modelos Moleculares , Conformação ProteicaRESUMO
BACKGROUND: Investigations using the Medical Outcomes Study Short Form 36 Healthy Survey (SF-36) and the American Orthopaedic Foot & Ankle Society Diabetic Foot Questionnaire (AOFAS-DFQ) have demonstrated a poor quality of life in patients with Charcot foot arthropathy. The Short Musculoskeletal Function Assessment (SMFA) questionnaire has been widely used in patients with a broad range of musculoskeletal disorders. METHODS: Twenty-five consecutive patients undergoing operative correction for diabetes-related Charcot foot arthropathy of the midfoot completed the SMFA prior to undergoing surgery. There were 16 males and 9 females. The average body mass index (BMI) was 37.4 (range 25.8-50.2), and the average hemoglobin A1c was 7.5 (range 5.3-10.1) prior to surgery. RESULTS: All 25 patients exhibited significant impairment in all 6 domains of the SMFA ( P < .0001) as compared to the normative data. There was a high correlation between each of the 6 domains of the SMFA, even after correcting for BMI. CONCLUSION: Charcot foot severely impaired the quality of life in patients beyond the impact of morbid obesity. This impairment equally impacted all of the functional and emotional domains measured with the SMFA as compared with population norms. This investigation provides a benchmark for measuring the impact of operative correction of the deformity. In addition, the SMFA appears to be a valid tool for measuring impairment in this complex patient population. LEVEL OF EVIDENCE: Level II, prospective comparative investigation.