Correlation between the release of IL-2 and granule-associated DNase activity in human lymphomononuclear cells stimulated with immunomodulating peptides and proteins. Role of different antigen-presenting cells.
The authors have already described that a series of short peptides, modelled after sequences related to human extracellular matrix (ECM) proteins and sharing some common structural features, activate Th1 clones through a process involving peptide presentation in HLA-DR proteins. Those peptides induce also LAK- and NK-dependent cytotoxicity as well as activation of monocytes/macrophages present in human peripheral blood mononuclear cell (PBMC) populations. The release of interleukin 2 (IL-2) and interferon gamma (IFN-gamma) by Th cells present in PBMC depleted of macrophages, or B cells is reported, after incubation in the presence of those peptides, fibronectin or Staphylococcus aureus protein A. The authors found that all the molecules tested needed at least the presence of a type of antigen-presenting cell (APC) to exert their stimulatory effect. Some peptides seem to be preferentially presented to Th cells by B cells, while others seem to depend on monocyte/macrophages for this presentation. The dependence on one or another APC seems to be due to differences in the sequences of these peptides. The immunomodulatory agents studied also gave rise to a clear increase in a DNase activity associated with secretion granules of PBMC. That there is a correlation between the release of IL-2 and this DNase activity when using a complete PBMC population, B cell-depleted PBMC or macrophage-depleted PBMC stimulated with the peptides tested has been found.
Migliaccio
M
M
Department of Biochemistry, University of Navarra, Pamplona, Spain.
Santiago
E
E
López-Moratalla
N
N
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism; D002469:Cell Separation; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000201:enzymology*; D003851:Deoxyribonucleases / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism
D000276:Adjuvants, Immunologic; D016326:Extracellular Matrix Proteins; D007376:Interleukin-2; D007371:Interferon-gamma; D003851:Deoxyribonucleases