Chronic alpha1-adrenoreceptor blockade produces age-dependent changes in rat thymus structure and thymocyte differentiation.
In order to examine the influence of chronic alpha1-adrenergic receptor (alpha1-AR) blockade on the thymus structure and T-cell maturation, peripubertal and adult male rats were treated with urapidil (0.20 mg/kg BW/d; s.c.) over 15 consecutive days. Thymic structure and phenotypic characteristics of the thymocytes were assessed by stereological and flow cytometry analysis, respectively. In immature rats, treatment with urapidil reduced the body weight gain and, affecting the volume of cortical compartment and its cellularity decreased the organ size and the total number of thymocytes compared to age-matched saline-injected controls. The percentage of CD4+8- single positive (SP) thymocytes was decreased, while that of CD4-8+ was increased suggesting, most likely, a disregulation in final steps of the positively selected cells maturation. However, alpha1-AR blockade in adult rats increased the thymus weight as a consequence of increase in the cortical size and cellularity. The increased percentage of most immature CD4-8- double negative (DN) cells associated with decreased percentage of immature CD4+8+ double positive (DP) thymocytes suggests a decelerated transition from DN to DP stage of T-cell development. As in immature rats, the treatment in adult rats evoked changes in the relative numbers of SP cells, but contrary to immature animals, favoring the maturation of CD4+8- over CD4-8+ thymocytes. These results demonstrate that: i) chronic blockade of alpha1-ARs affects both the thymus structure and thymocyte differentiation, ii) these effects are age-dependent, pointing out to pharmacological manipulation of alpha1-AR-mediated signaling as potential means for modulation of the intrathymic T-cell maturation.
Plećas-Solarović
B
B
Department of Physiology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia and Montenegro. bplecas@pharmacy.bg.ac.yu
Hristić-Zivković
I
I
Radojević
K
K
Kosec
D
D
Leposavić
G
G
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000367:Age Factors; D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects*; D048429:Cell Size / Q000187:drug effects; D005434:Flow Cytometry; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D013601:T-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D013950:Thymus Gland / Q000033:anatomy & histology / Q000166:cytology / Q000187:drug effects*
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D015704:CD4 Antigens; D016827:CD8 Antigens; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D016693:Receptors, Antigen, T-Cell, alpha-beta; C015568:urapidil