ABSTRACT
Bovine serum albumin (BSA) and the surface A-layer protein (AP) of an atypical strain of fish bacterial pathogen Aeromonas salmonicida were covalently linked with polymeric nano- and microparticles, and antigenicity of the resulted conjugates was compared in mice and goldfish. Distinct albeit different levels of natural BSA and AP antibodies were present in both animal species. Significant stimulation of the anti-AP antibody response in mice strikingly contrasted to unresponsiveness or even suppression in fish. The results negatively correlate with the levels of respective natural antibodies in the host and are discussed in context of problems related to fish vaccination. The work reinforces the instructive role of natural antibodies in adaptive immune response.
Subject(s)
Adjuvants, Immunologic/pharmacology , Antibodies/chemistry , Antibodies/immunology , Antigens, Bacterial/chemistry , Antigens, Bacterial/immunology , Nanoparticles , Vaccines/immunology , Acrolein/chemistry , Acrolein/immunology , Adjuvants, Immunologic/chemistry , Aeromonas salmonicida/growth & development , Aeromonas salmonicida/immunology , Aluminum Compounds/pharmacology , Animals , Antigens/immunology , Cattle , Chemistry, Pharmaceutical , Drug Design , Emulsions , Goldfish/immunology , Indicators and Reagents , Mice , Mice, Inbred BALB C , Nanoparticles/chemistry , Polymers/chemistry , Sepharose/chemistry , Serum Albumin, Bovine/immunology , Vaccines/administration & dosageABSTRACT
The JAK-STAT signal transduction cascade participates in various cellular processes, including immune response, cell replication, differentiation and oncogenesis. Here, we report that this cascade is induced in two human myeloid HL-60 leukemia cell variants by the granulocyte differentiation inducer dimethyl sulfoxide (DMSO) and macrophage differentiation inducer phorbol 12-myristate 13-acetate (PMA). DMSO and PMA also induced the expression and catalytic activity of 2'-5' oligoadenylate synthetase (2-5A synthetase), a known interferon (IFN) inducible enzyme. The HL-60 cell variants included HL-205, which is susceptible to DMSO- and PMA-induced differentiation, and HL-525, which is susceptible to DMSO- but not to PMA-induced differentiation. Treatment of HL-205 and HL-525 cells with DMSO and HL-205 cells with PMA-induced JAK1 phosphorylation, JAK1/STAT1 association, formation of STAT1-STAT2 heterodimers, and the binding of the active IFN stimulating growth factor 3 (ISGF3) to the IFN-stimulated response element (ISRE) fragment isolated from the 2-5A synthetase promoter. These events were either reduced or absent in the resistant HL-525 cells treated with PMA. Taken together, our data implicate the above signaling cascade in DMSO- and PMA-induced 2-5A synthetase expression and catalytic activity in the HL-60 cell system.
