27 December 2002
Characterization of dendritic cells generated in vivo by an E. coli derived chimeric dual receptor agonist.
Larry E. Kahn, Parul Doshi, Kelly L. McGarity, Mingfu Yu, Christine P. Bono, Wen-Rong Lie, Anne M. Rankin, Mary L. Smidt, Philip R. Streeter, Barbara K. Klein, Joseph K. Welply, Susan L. WoulfeMed Sci Monit 2002; 8(12): BR504-514 :: ID: 4819
Abstract
BACKGROUND: Progenipoietin-4 (ProGP-4) is an E. coli derived chimeric growth factor that activates the human Flt3 and G-CSF receptors. ProGP-4 possesses cross-species activity and treatment of mice with ProGP-4 results in increases in the number of WBC and Class II+/CD11c+ cells in both spleen and peripheral blood. Herein, we report morphologic, phenotypic and functional evaluation of Class II+/CD11c+ cells generated by in vivo administration of ProGP-4. MATERIAL/METHODS: C57BL/6 mice were injected daily with ProGP for 7 to 18 days. Leukocytes from spleen and peripheral blood were analyzed by flow cytometry to enumerate and characterize changes in DC populations. Spleens from ProGP treated mice were evaluated by immunocytochemistry and enriched CD11c+ populations were functionally assessed in a mixed lymphocyte assay and in an antigen dependent CTL assay. RESULTS: Administration of this dual receptor agonist to mice resulted in dose-dependent increases in the numbers of total white blood cells and Class II+/CD11c+ cells in spleen and peripheral blood. CD11c+ cells from ProGP-4 treated mice co-expressed DEC205 and also expressed CD80, CD86 and CD40, albeit at lower levels as compared to Class II+/CD11c+ cells from untreated animals. Despite lower co-stimulatory molecule expression, ProGP-4-generated Class II+/CD11c+ cells stimulated proliferation of allogeneic T cells and an antigen-specific T cell hybridoma as efficiently as bone marrow derived dendritic cells from untreated mice. CONCLUSIONS: The data presented in this report highlight the ability of E. coli derived ProGP-4 to expand large numbers of functional DC in the peripheral blood and lymphoid organs in vivo using a rodent model of hematopoiesis. E. coli derived chimeric receptor agonists such as ProGP-4 may enable further investigations of immunotherapeutic approaches to the treatment of diseases such as cancer and autoimmunity.
Keywords: Antigens, CD11c - metabolism, Colony-Stimulating Factors - pharmacology, Proto-Oncogene Proteins - agonists, Receptors, Granulocyte Colony-Stimulating Factor - agonists
Most Viewed Current Articles
13 Apr 2020 : Original article
Outcome of 24 Weeks of Combined Schroth and Pilates Exercises on Cobb Angle, Angle of Trunk Rotation, Chest...DOI :10.12659/MSMBR.920449
Med Sci Monit Basic Res 2020; 26:e920449
11 May 2020 : Original article
Analysis of Psychological and Sleep Status and Exercise Rehabilitation of Front-Line Clinical Staff in the ...DOI :10.12659/MSMBR.924085
Med Sci Monit Basic Res 2020; 26:e924085
05 Jan 2021 : Review article
A Southeast Asian Perspective on the COVID-19 Pandemic: Hemoglobin E (HbE)-Trait Confers Resistance Against...DOI :10.12659/MSMBR.929207
Med Sci Monit Basic Res 2021; 27:e929207
10 Aug 2020 : Clinical Research
Effects of Cognitive Task Training on Dynamic Balance and Gait of Patients with Stroke: A Preliminary Rando...DOI :10.12659/MSMBR.925264
Med Sci Monit Basic Res 2020; 26:e925264