The Structure of the Chemokine Receptor CXCR1 in Phospholipid Bilayers and Interactions with IL-8

CXCR1 is one of two high-affinity receptors for the CXC chemokine interleukin-8 (IL-8), a major mediator of immune and inflammatory responses implicated in many disorders, including tumor growth(1-3). IL-8, released in response to inflammatory stimuli, binds to the extracellular side of CXCR1. The ligand-activated intracellular signaling pathways result in neutrophil migration to the site of inflammation(2). CXCR1 is a class-A, rhodopsin-like G-protein-coupled receptor (GPCR), the largest class of integral membrane proteins responsible for cellular signal transduction and targeted as drug receptors(4-7). Despite its importance, its molecular mechanism is poorly understood due to the limited structural information available. Recently, structure determination of GPCRs has advanced by tailoring the receptors with stabilizing mutations, insertion of the protein T4 lysozyme and truncations of their amino acid sequences(8), as well as addition of stabilizing antibodies and small molecules(9) that facilitate crystallization in cubic phase monoolein mixtures(10). The intracellular loops of GPCRs are critical for G-protein interactions(11) and activation of CXCR1 involves both N-terminal residues and extracellular loops(2,12,13). Our previous NMR studies indicate that IL-8 binding to the N-terminal residues is mediated by the membrane, underscoring the importance of the phospholipid bilayer for physiological activity(14). Here we report the three-dimensional structure of human CXCR1 determined by NMR spectroscopy. The receptor is in liquid crystalline phospholipid bilayers, without modification of its amino acid sequence and under physiological conditions. Features important for intracellular G-protein activation and signal transduction are revealed

Cesarean delivery among nulliparous women in Beirut: assessing predictors in nine hospitals.

BACKGROUND: Obstetric practice has witnessed a worldwide trend of increasing cesarean section rates in recent years. Similar trends have been observed in Lebanon, according to 2 studies conducted in 1996 and 1999. The objective of the present study was to assess the differences in predictors of cesarean delivery among nulliparous women in a "control hospital" with a low cesarean delivery rate (12.5%) and the rest of the National Collaborative Perinatal Neonatal Network (NCPNN) "study hospitals" with a higher cesarean delivery rate (31.4%). METHODS: Data were collected by the NCPNN database, which covers deliveries at 9 major hospitals located in the Greater Beirut area. Data analysis was performed on the 6,668 consecutive deliveries occurring between January 1, 2001, and December 31, 2002, at the NCPNN participating centers. The questionnaires included items that cover parental sociodemographic characteristics and maternal and newborn health characteristics. Sources of data included direct interviews with mothers after delivery and before hospital discharge and reviews of obstetric and nursery medical charts. Chi-square tests and t tests were performed for categorical and continuous clinical predictors of cesarean section. Logistic regression was performed to determine the odds of having a cesarean section for the study hospitals when compared with the control hospital. Odds ratios and 95% confidence intervals are reported. RESULTS: Variables in the study hospitals that correlated with a higher cesarean delivery rate were male obstetricians, day of the week, and mode of payment compared with the control hospital. CONCLUSIONS: In a country with a high cesarean section rate, 1 hospital met World Health Organization criteria for acceptable cesarean section rates, with no compromise in neonatal outcome. Further studies are needed to investigate potential policies to decrease the high cesarean section rate