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A Melendez

Publications and source records attributed to A Melendez.

5 recordsLinked to original sources
PubMed1998

FcgammaRI coupling to phospholipase D initiates sphingosine kinase-mediated calcium mobilization and vesicular trafficking.

Aggregation of receptors specific for the constant region of immunoglobulin G activates a repertoire of monocyte responses that can lead ultimately to targeted cell killing via antibody-directed cellular cytotoxicity. The high affinity receptor, FcgammaRI, contains no recognized signaling motif in its cytoplasmic tail but rather utilizes the gamma-chain of FcepsilonRI as an accessory molecule to recruit tyrosine kinases for signal transduction. We show here that, in a human monocytic cell line primed with interferon-gamma, FcgammaRI mobilizes intracellular calcium stores using a novel pathway that involves tyrosine kinase coupling to phospholipase D and resultant downstream activation of sphingosine kinase. Moreover, FcgammaRI is not coupled to phospholipase C; hence, calcium release from intracellular stores occurred in the absence of any measurable rise in inositol triphosphate. Finally, as this novel activation pathway is also shown to be responsible for mediating the vesicular trafficking of internalized immune complexes for degradation, it is likely to play a key role in controlling intracellular events triggered by FcgammaRI.

Antibodies, Monoclonal↗
PubMed1998

A molecular switch changes the signalling pathway used by the Fc gamma RI antibody receptor to mobilise calcium.

BACKGROUND: Leukocytes express Fc gamma receptors, which are specific for the constant region of immunoglobulin G. Aggregation of these receptors activates a repertoire of responses that can lead to targeted cell killing by antibody-directed cellular cytotoxicity. The nature of the myeloid response to Fc gamma receptor aggregation is highly variable and depends on the maturation state of the cell, but little is known about the signalling mechanisms underlying this variability. RESULTS: We show here that differentiation of a monocytic cell line, U937, to a more macrophage phenotype resulted in an absolute and fundamental switch in the nature of the phospholipid signalling pathway recruited following Fc gamma receptor aggregation. In cytokine-primed monocytes, aggregation of the high-affinity receptor Fc gamma RI resulted in the activation of phospholipase D and sphingosine kinase, which in turn led to the transient release of stored calcium; these effects were mediated by the gamma chain, an Fc gamma RI accessory protein. In contrast, in cells differentiated to a more macrophage type, aggregation of Fc gamma RI resulted in the Fc gamma RIIa-mediated activation of phospholipase C, and the resulting calcium response was prolonged as calcium entry was stimulated. CONCLUSIONS: The switch in Fc gamma RI signalling pathways upon monocyte differentiation is mediated by a switch in the accessory molecule recruited by Fc gamma RI, which lacks its own intrinsic signal transduction motif. As many immune receptors have separate polypeptide chains for ligand binding and signal transduction (allowing a similar switch in signalling pathways), the mechanism described here is likely to be widely used.

Bucladesine↗
PubMedDate not supplied

Single-pass continuous flow peritoneal dialysis using two catheters.

With a renewed interest in continuous flow peritoneal dialysis (CFPD), our standard practice of implanting a second catheter in those patients facing access failure provided us the opportunity to perform acute studies on CFPD in these patients, since it temporarily provided us with two catheters. Four patients were studied, with a total of five studies performed. A standard protocol was followed utilizing 1.5% dextrose solution, a 2 L fill, an inflow rate of 200 ml/min with a proportionate outflow for a 4-hour session. A full drain was performed at the end of the study. Our results provided us with a mean effective peritoneal clearance for urea (KpeU) and creatinine (KpeCr) of 40 ml/min and 28 ml/min, respectively, and a mean ultrafiltration rate (Qf) of 13.4 ml/min. Our average mass transfer coefficient (MTC) for urea was 40 ml/min, consistent with kinetic modeling and historical data. The Kpe, MTC, and Qf achieved are significantly higher than other investigators, which could possibly be explained by those obtained by two separate catheters resulting in adequate mixing of the dialysate. These clinical results provide a solid foundation for the future development of this PD modality.

Catheterization↗