Subject(s)
Oligopeptides/metabolism , Oligopeptides/physiology , T-Lymphocytes/metabolism , Culture Media, Conditioned/pharmacology , Dose-Response Relationship, Drug , HL-60 Cells , Humans , Immunoenzyme Techniques , Interleukin-2/metabolism , Kinetics , Models, Biological , Neoplasms/immunology , Protein BindingABSTRACT
Myelopeptides are immunoregulatory molecules originally isolated from porcine bone marrow cell culture. The influence of synthetic analogous of these peptides on IL-1 and IL-2 activities was studied. Myelopeptide-1 but not myelopeptide-2 replaced IL-1 activity in a test of costimulation of thymocyte proliferation in the presence of mitogen. Conversely, myelopeptide-2, but not myelopeptide-1, stimulated both production of IL-2 by murine splenocytes and IL-2-dependent proliferation of CTLL-2 cell line. The enhancing effect of myelopeptide-2 on IL-2-associated processes was the most pronounced at the early stages of cell activation. The resting T cells stimulated with suboptimum doses of concanavalin A and activated T cells, expressing low level of IL-2R, were sensitive to myelopeptide-2 action. The possible role of myelopeptides in differentiation of T0 helper into T1 helper and T2 helper is discussed.
ABSTRACT
Bone marrow myelopeptides (MP), besides having immunostimulatory activity, had a pronounced dose-dependent effect on the development of pain sensitivity in mice. Nanogram amounts of MP evoked a hyperalgesic response and increased antibody formation to sheep red blood cells three to nine times. Milligram amounts of MP had a hypoalgesic effect and did not affect antibody response. Opioid peptides derived from the bone marrow MP are involved in the expression of the antibody response, and a mixture of synthetic opioids, corresponding in composition to that found in natural MP, stimulated antibody production. The antibody-stimulating effect of MP was abolished by naloxone. Of the opioid peptides, only beta-endorphin showed antibody-stimulating activity. On reversed-phase chromatography the antibody-stimulating peptides and beta-endorphin were eluted in different fractions, indicating that the immunostimulatory and opioid activities are produced by different peptide molecules.