title: High levels of filamentous actin and apoptosis correlate with mast cell refractoriness under alloxan-evoked diabetes.
abstract: Mast cell number and reactivity were shown to be down-regulated under diabetic conditions. Since the balance between globular and filamentous actin plays a pivotal role in the activity of secretory cells, we investigated whether an imbalance in that system could underlie the hyporesponsiveness of mast cells in diabetes. The apoptotic state was also evaluated. By means of rhodamine/phalloidine staining of F-actin, we noted that diabetic mast cells exhibited an increase in fluorescence intensity and reduction in cellular size, when compared with cells from normal animals, in parallel with elevation in the percentage of cells developing apoptosis. The levels of Bax, a pro-apoptotic member of Bcl-2 family, appeared increased at baseline in mast cells from diabetic rats compared with normal cells. These phenomena correlated with reduction in histamine and PGD2 release following antigen challenge in vitro. The steroid antagonist RU 486 abolished the reduction of histamine secretion from diabetic mast cells. We conclude that hyporesponsiveness of mast cells noted in diabetes may be accounted for by reduction in actin filament plasticity, in clear association with the rise in the percentage of cells undergoing apoptosis. In addition, the refractoriness of diabetic mast cells to antigen in vitro seems to be dependent on glucocorticoids.
authors.affiliation: Laboratory of Inflammation, Department of Physiology and Pharmacodynamics, Brazil.
authors.forename: Emiliano O
authors.initials: EO
authors.lastname: Barreto
authors.forename: Vinícius F
authors.initials: VF
authors.lastname: Carvalho
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Oliveira
authors.forename: Alvaro L
authors.initials: AL
authors.lastname: Bertho
authors.forename: Thereza C
authors.initials: TC
authors.lastname: Barja-Fidalgo
authors.forename: Renato S B
authors.initials: RS
authors.lastname: Cordeiro
authors.forename: Marco A
authors.initials: MA
authors.lastname: Martins
authors.forename: Patrícia M R
authors.initials: PM
authors.lastname: e Silva
mesh_terms: D000019:Abortifacient Agents / Q000494:pharmacology; D000199:Actins / Q000378:metabolism* / Q000648:ultrastructure*; D000315:Adrenalectomy; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002469:Cell Separation; D047630:Depsipeptides / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology*; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000502:physiology; D006636:Histamine Release / Q000187:drug effects; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D008856:Microscopy, Fluorescence; D015735:Mifepristone / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000019:Abortifacient Agents; D000199:Actins; D000970:Antineoplastic Agents; D001786:Blood Glucose; D047630:Depsipeptides; D005938:Glucocorticoids; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C057531:jasplakinolide; D015735:Mifepristone; D015230:Prostaglandin D2