Syntaxin-4 is implicated in the secretion of antibodies by human plasma cells.

PCs are responsible for the production and secretion of antibodies, the effector molecules of the humoral immune response. The molecular mechanisms responsible for vesicle docking and secretion implicated in the antibody-secretion process are not well-known, as they have not been studied, but it is known that SNARE proteins are responsible for many membrane-fusion processes in the cell. We show here that freshly isolated human colon LP-PCs and T-PCs from MM-PC patients and the U266 cell line, as a model for PC secretion, contain a set of these proteins. SNAP23, STX3, and STX4 were localized mainly in the plasma membrane of PCs, and interactions of SNAP23 with STX3 and with STX4 were proven by IP. Interaction between SNAP23 and STX4 was also confirmed in situ. With the use of siRNA, as well as shRNA, the functional role of SNAP23, STX3, and STX4 in antibody secretion was also examined. The findings demonstrate that in addition to SNAP23, STX4 is implicated in the antibody secretion by a myeloma cell line and by normal human colon LP-PCs.

Identification of soluble N-ethylmaleimide-sensitive factor attachment protein receptor exocytotic machinery in human plasma cells: SNAP-23 is essential for antibody secretion.

Plasma cells (PC) are B-lymphocytes terminally differentiated in a postmitotic state, with the unique purpose of manufacturing and exporting Igs. Despite the importance of this process in the survival of vertebrates, no studies have been made to understand the molecular events that regulate Ig exocytosis by PC. The present study explores the possible presence of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) system in human PC, and examines its functional role in Ig secretion. Syntaxin-2, Syntaxin-3, Syntaxin-4, vesicle-associated membrane protein (VAMP)-2, VAMP-3, and synaptosome-associated protein (SNAP)-23 could be readily detected in normal human PC obtained from intestinal lamina propria and blood, as well as in human PC lines. Because SNAP-23 plays a central role in SNAREs complex formation, it was chosen to examine possible functional implications of the SNARE system in PC Ig secretion. When recombinant SNAP-23 fusion protein was introduced into the cells, a complete abolishment of Ig production was observed in the culture supernatants of PC lines, as well as in those of normal PC. These results provide insights, for the first time, into the molecular machinery of constitutive vesicular trafficking in human PC Ig secretion and present evidence indicating that at least SNAP-23 is essential for Ab production.

Rotura ureteral iatrogénica de causa inusual / Exceptional iatrogenic ureteral rupture

La rotura del uréter es una entidad clínica poco frecuente que puede ocasionar graves consecuencias. Su causa más habitual es la iatrogenia durante una intervención quirúrgica. Otras posibles causas son las maniobras urológicas o urográficas. En nuestra paciente, como caso único publicado hasta el momento, la rotura se ocasionó por un sondaje urinario traumático, al hinchar el balón de la sonda en el interior de un uréter. Los síntomas de la rotura uretral son los de un cólico nefrítico, aunque en ocasiones puede simular un abdomen agudo. Es importante valorar la posibilidad de lesión uretral en pacientes intervenidos de cirugía abdominopélvica o sometidos maniobras urológicas que presenten esta clínica. El tratamiento es quirúrgico, aunque en algunos casos podrían considerarse medidas conservadoras (AU)

Rupture of the ureter is an infrequent event that can have serious consequences. The most frequent cause is surgical iatrogenic ureter disease. Other possible causes are urological procedures and urographic studies. In our patient, which, to our knowledge, is the first to be reported in the literature, the ureteral rupture was produced by a traumatic urinary catheterism, because the balloon was filled inside the ureter. The normal presentation is nephritic colic, although acute abdomen is also a possibility. The possibility of ureteral rupture in abdominopelvic surgery or in urological techniques should be evaluated when patients present these clinical symptoms. Treatment is surgical, although in some cases conservative measures can be used (AU)

[Exceptional iatrogenic ureteral rupture]. / Rotura ureteral iatrogénica de causa inusual.

Rupture of the ureter is an infrequent event that can have serious consequences. The most frequent cause is surgical iatrogenic ureter disease. Other possible causes are urological procedures and urographic studies. In our patient, which, to our knowledge, is the first to be reported in the literature, the ureteral rupture was produced by a traumatic urinary catheterism, because the balloon was filled inside the ureter. The normal presentation is nephritic colic, although acute abdomen is also a possibility. The possibility of ureteral rupture in abdominopelvic surgery or in urological techniques should be evaluated when patients present these clinical symptoms. Treatment is surgical, although in some cases conservative measures can be used.

Differences in thyroid-infiltrating B lymphocytes in patients with Graves' disease: relationship to autoantibody detection.

OBJECTIVE: Thyroid-infiltrating B (Thyr-B) lymphocytes are thought to play an important role in the pathogenic mechanisms underlying Graves' disease. DESIGN AND METHODS: In this study, a broad phenotypic analysis of these cells has been performed in 15 consecutive patients who underwent thyroidectomy. RESULTS: Data reveal the occurrence of two distinct types of Thyr-B cell infiltrates. Type 1 was present in most of the cases (10/15) and consisted of a combination of IgM+ IgD(low to-) B lymphocytes showing features of marginal zone B cells, and IgG+ classic memory B cells. In contrast, in 5 of the 15 cases, a second type of Thyr-B cell infiltrate occurred, exhibiting the profile IgM- IgD- CD44(low to-) CD38++ CD71+ CD95+. This phenotype is highly suggestive of germinal center (GC) B cells, a finding not always anticipated from routine histologic examination. The presence of these ectopic GC was closely associated with the elevated serum level of anti-thyroid peroxidase (TPO), but not with anti-thyrotropin receptor (TSHR), autoantibodies. Moreover, local active anti-thyroglobulin (Tg) antibody secretion was only detected in cultures of type 2 Thyr-B cells. CONCLUSION: These findings indicate that high titers of anti-TPO, but not anti-TSHR antibody, might be associated with intrathyroidal GC development.

Purification of human lamina propria plasma cells by an immunomagnetic selection method.

Plasma cells (PC) are the terminal stage of B-lymphocyte differentiation and, as such, they are dedicated to large-scale secretion of antibodies (Ab). Bone marrow (BM) and lamina propria (LP) become the final reservoirs of PC generated in response to systemic and mucosal antigen stimulation, respectively. Although the majority of human PC are held in the mucosa LP, they have received less attention than PC present in other locations. A key step for many PC studies is the design of isolation protocols to purify them. A purification procedure for LPPC has not been described as yet and, therefore, we decided to develop a protocol for this purpose, comprising three main steps: (1) dissecting LP from colonic tissue; (2) releasing LP cells by a short 15-min collagenase digestion; (3) isolating LPPC by positive immuno-magnetic selection using the distinctive expression of CD54 (ICAM-I) on LPPC. By following this protocol, a viable, highly purified LPPC fraction can be obtained in less than 2 1/2 h.