Differential expression and secretion of RANTES and MCP-1 in activated peripheral blood mononuclear cell cultures of atopic subjects.

RANTES and MCP-1 represent a link between the activation of monocytes, lymphocytes, basophils, mast cells and eosinophils in inflammatory disorders, such as the late phase allergic reaction. These C-C chemokines also play a role in regulating Th cell cytokine production and leukocyte trafficking. In this study, we determined the expression and secretion of RANTES and MCP-1 from PHA-activated PBMC of healthy and atopic subjects with no symptoms. Levels of RANTES from PHA-activated PBMC of atopic patients were higher, at 18 and 24 h incubations (42+/-5.5 and 48+/-4), compared to controls (20+/-4 and 35+/-4), respectively; while MCP-1 was not (12+/-3 and 17+/-3) compared to controls (10.5+/-3 and 15+/-2), respectively. This effect was also revealed on RANTES mRNA expression, as determined by reverse transcriptase polymerase chain reaction (RT-PCR) analysis. In addition, PHA-activated PBMC of atopic subjects produce more IL-4 (five times more) than healthy subjects, while IFN-gamma did not vary. RANTES, compared to MCP-1, may have more influence on signal transduction pathways, either in physiologic or inflammatory states and may induce profound effects on the regulation of cell activity. The differential production of RANTES and MCP-1 may lead to diverse regulation of the function and development of cells involved in the allergic response. These studies emphasize the importance of chemokine selectivity during inflammation.

MCP-1 and RANTES are mediators of acute and chronic inflammation.

Regulation of leukocyte migration and activation by chemokines are recognized as potentially important functions in the induction of acute and chronic inflammatory reactions. Regulated upon activation normal T cell expressed and presumably secreted (RANTES), monocyte chemotactic protein-1 (MCP-1), and related molecules constitute the C-C class of the beta chemokine supergene family with inflammatory properties. Here we report that in experimental studies RANTES and MCP-1 provoke mast cell activation and increase histidine decarboxylase mRNA expression in a dose-dependent manner. Moreover, injections of RANTES and MCP-1 in the rat skin cause mast cell, eosinophil, and macrophage recruitment, and prostaglandin E2 (PGE2) generation. In a chronic inflammatory model MCP-1 was found to mediate the recruitment of mononuclear cells in calcified granulomas. In addition, MCP-1 mediated parasitic infections caused by Trichinella spiralis. In accordance with other studies, RANTES and MCP-1 were found to play an important role in the lung allergic inflammation, lung leukocyte infiltration, bronchial hyperresponsiveness, and the recruitment of eosinophils in the pathogenesis of asthma. Here for the first time we propose a new mechanism of pulmonary airway inflammation where RANTES and MCP-1 are deeply involved. We also studied the apparent role played by RANTES in the pathogenesis of relapsing-remitting multiple sclerosis enhancing the inflammatory response within the nervous system.

Effects of cimetropium bromide on gallbladder contraction in response to oral and intraduodenal olive oil.

To evaluate the influence of the stomach and the cholinergic system on gallbladder contraction induced by physiological stimuli, the reduction in gallbladder volume in 7 healthy volunteers has been studied by real-time ultrasonography after the oral and intraduodenal administration of olive oil, preceded by pretreatment with cimetropium bromide or placebo. After an overnight fast, each subject swallowed 50 ml olive oil or it was administered through a naso-duodenal tube in the proximal duodenum. Cimetropium bromide 5 mg or placebo was given intravenously under double-blind control. After the placebo pretreatment, gallbladder contraction was greater and faster after intraduodenal oil than after oral oil. Cimetropium bromide decreased the extent, velocity and duration of gallbladder contraction induced by intraduodenal olive oil but it only reduced the velocity of the contraction induced by oil given orally. It is concluded that in normal human subjects the stomach modulates the extent and velocity of postprandial gallbladder contraction and that anticholinergic agents antagonize the gastric and duodenal phases of the response of the gallbladder to a meal.