INTRODUCTION : Plasma cell dyscrasias are immunosecretory disorders that can lead to haematological malignancies such as Multiple Myeloma (MM). Monoclonal immunoglobulin Free Ught Chains (FLC) are present in the serum and urine of many patients with plasma celi diseases. FLCs producing cells and paraproteins themselves are able to induce different tissue damage. Studies demonstrate that exosomes can modulate immune-regulatory processes, set up tumor estape mechanisms, and transfer physiological information, thus we investigated if FLCs are processed via microvesicles in the blood stream. METHODS: Serum samples from MM, Amyloidosis AL and Monoclonal gammopathy of undetermined significance (MGUS) patients were collected. We established an experimental protocol to test microvesicles release in endothelial and myocardial FLCs treated cells. The celi culture medium and serum samples were processed by utracentrifugation, density gradient separation and immunoaffinity capture beads. We analysed the microvesicles/exosomes profile with protein quantification, western blot analysis and thin layer cromatography. RESULTS: We show that after internalization, FLCs are rerouted in the extracellular space via microvesicles/exosomes that could be re-internalized in contiguous cells. The isolated serum vesicles from MM, AL Amyloidosis and MGUS patients contained FLCs and were strongly positive for Hsp70, annexin 5 and c-src compared to MGUS and controls. CONCLUSION: In the present study we reveal a novel mechanism of FLCs processing that involves c-src labeled extracellular vesicles. This evidences suggest a novel mechanism of c-src activation during plasma celi dyscrasia and its involvement in proinflammatory events and tissue damage. The in vitro data are strongly confirmed by characteristics of in vivo produced microvesicles. More strikingly MGUS derived microvesicles are different from those patients with MM or AL Amyloidosis, suggesting a new prognostic tool.
Microvesicles Mediated Trafficking of Immunoglobulin Free Light Chains.
DI NOTO, Giuseppe;PAOLINI, Lucia;RICOTTA, Doris
2013-01-01
Abstract
INTRODUCTION : Plasma cell dyscrasias are immunosecretory disorders that can lead to haematological malignancies such as Multiple Myeloma (MM). Monoclonal immunoglobulin Free Ught Chains (FLC) are present in the serum and urine of many patients with plasma celi diseases. FLCs producing cells and paraproteins themselves are able to induce different tissue damage. Studies demonstrate that exosomes can modulate immune-regulatory processes, set up tumor estape mechanisms, and transfer physiological information, thus we investigated if FLCs are processed via microvesicles in the blood stream. METHODS: Serum samples from MM, Amyloidosis AL and Monoclonal gammopathy of undetermined significance (MGUS) patients were collected. We established an experimental protocol to test microvesicles release in endothelial and myocardial FLCs treated cells. The celi culture medium and serum samples were processed by utracentrifugation, density gradient separation and immunoaffinity capture beads. We analysed the microvesicles/exosomes profile with protein quantification, western blot analysis and thin layer cromatography. RESULTS: We show that after internalization, FLCs are rerouted in the extracellular space via microvesicles/exosomes that could be re-internalized in contiguous cells. The isolated serum vesicles from MM, AL Amyloidosis and MGUS patients contained FLCs and were strongly positive for Hsp70, annexin 5 and c-src compared to MGUS and controls. CONCLUSION: In the present study we reveal a novel mechanism of FLCs processing that involves c-src labeled extracellular vesicles. This evidences suggest a novel mechanism of c-src activation during plasma celi dyscrasia and its involvement in proinflammatory events and tissue damage. The in vitro data are strongly confirmed by characteristics of in vivo produced microvesicles. More strikingly MGUS derived microvesicles are different from those patients with MM or AL Amyloidosis, suggesting a new prognostic tool.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
