ABSTRACT
ß-Cell plasticity governs the adjustment of ß-cell mass and function to ensure normoglycemia. The study of how ß-cell mass is controlled and the identification of alternative sources of ß-cells are active fields of research. ß-Cell plasticity has been implicated in numerous physiological and pathological conditions. We developed a mice model in which we induced major ß-cell mass atrophy by implanting insulin pellets (IPI) for 7 or 10 days. The implants were then removed (IPR) to observe the timing and characteristics of ß-cell regeneration in parallel to changes in glycemia. Following IPR, the endocrine mass was reduced by 60% at day 7 and by 75% at day 10, and transient hyperglycemia was observed, which resolved within 1 wk. Five days after IPR, enhanced ß-cell proliferation and an increased frequency of small islets were observed in 7-day IPI mice. ß-Cell mass was fully restored after an additional 2 days. For the 10-day IPI group, ß-cell and endocrine mass were no longer significantly different from those of the control group at 2 wk post-IPR. Furthermore, real-time quantitative PCR analysis of endocrine structures isolated by laser capture microdissection indicated sequentially enhanced expression of the pancreatic transcription factors ß(2)/NeuroD and Pdx-1 post-IPR. Thus, our data suggest this mouse model of ß-cell plasticity not only relies on replication but also involves enhanced cell differentiation plasticity.
Subject(s)
Hypoglycemia/chemically induced , Hypoglycemic Agents/pharmacology , Insulin-Secreting Cells , Insulin/pharmacology , Islets of Langerhans , RNA, Messenger/analysis , Animals , Apoptosis/drug effects , Apoptosis/physiology , Cell Enlargement/drug effects , Cell Proliferation , Congenital Hyperinsulinism , Female , Glucose/metabolism , Glucose Transporter Type 2/metabolism , Insulin-Secreting Cells/drug effects , Insulin-Secreting Cells/pathology , Insulin-Secreting Cells/physiology , Islets of Langerhans/cytology , Islets of Langerhans/drug effects , Islets of Langerhans/physiology , Laser Capture Microdissection , Mice , Nesidioblastosis , Polymerase Chain Reaction , Regeneration/drug effects , Regeneration/physiology , Time Factors , Transcription Factors/metabolismSubject(s)
CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Chemokine CX3CL1/biosynthesis , Hypertension, Pulmonary/blood , Hypertension, Pulmonary/complications , Pulmonary Artery/pathology , Adult , Airway Obstruction , Case-Control Studies , Female , Hemodynamics , Humans , Inflammation , Lung/pathology , Male , Middle Aged , PhenotypeABSTRACT
Secretory immunoglobulin A (S-IgA) participates in the first noninflammatory line of defence of the respiratory tract. S-IgA consists of dimeric IgA (dIgA) produced by plasma cells and secretory component (SC) produced by epithelial cells. This study compared SC production by primary cultures of human bronchial epithelial cells (HBEC) and by respiratory epithelial cell lines. Among the cell lines, A549 did not produce detectable SC, 16HBE produced very low levels of SC, while CALU-3 produced significant levels of SC. HBEC produced SC in nonpolarized and polarized primary cultures, where it was secreted apically. Polarized HBEC transcytosed radiolabelled and cold dIgA, resulting in the presence of S-IgA in their apical media. SC production and IgA transcytosis by polarized HBEC were upregulated by interferon-gamma (IFN-gamma) after 48 h. By reverse transcription-polymerase chain reaction, no SC messenger ribonucleic acid (mRNA) was detected in A549 and 16HBE, while SC mRNA in CALU-3 was comparable to that of HBEC incubated for 48 h with IFN-gamma. By immunocytochemistry, HBEC expressed SC immunostaining and its intensity increased after 48 h with IFN-gamma. It is concluded that human bronchial epithelial cells produce secretory component and transcytose dimeric immunoglobulin A in vitro. These processes were apically polarized and upregulated by interferon-gamma. Among the cell lines studied, only CALU-3 expressed secretory component-messenger ribonucleic acid and produced detectable secretory component.
