ABSTRACT
The calprotectin (MRP8/14) protein complex belongs to the S100 family of Ca2+ binding proteins and is expressed during myelomonocytic differentiation. MRP8/14 plasma levels were determined by ELISA in 35 patients with active pulmonary tuberculosis (TB) showing mild (n = 12), moderate (n = 11) or severe (n = 12) disease, 13 patients with active pulmonary sarcoidosis (SR) and 21 healthy controls. TB patients had significantly increased plasma levels of MRP8/14 in comparison with SR and controls, which significantly depended on the volume of lung tissue involved in the inflammatory process. In TB patients, there was no correlation between plasma levels of MRP8/14 and total white blood cell (WBC) count, and blood polymorphonuclear neutrophil (PMN) count. In SR patients, MRP8/14 plasma levels were twofold higher in comparison with controls, but were lower compared with mild TB, and correlated with PMN and WBC counts. Human monocytes infected and cultured for 7 days with Mycobacterium bovis bacillus Calmette-Guérin showed fivefold higher MRP8/14 levels in supernatants compared with unstimulated or purified protein derivative-stimulated cells. Human MRP8/14 significantly increased Mycobacterium tuberculosis H37Rv growth in liquid medium in a dose- and time-dependent manner. These findings suggest that MRP8/14 plays an important role in the immunopathogenesis of tuberculosis.
Subject(s)
Membrane Glycoproteins/blood , Neural Cell Adhesion Molecules/blood , Sarcoidosis, Pulmonary/immunology , Tuberculosis, Pulmonary/immunology , Tuberculosis, Pulmonary/physiopathology , Blood Cell Count , Cells, Cultured , Culture Media , Humans , Inflammation , Leukocyte L1 Antigen Complex , Membrane Glycoproteins/pharmacology , Monocytes/immunology , Monocytes/microbiology , Mycobacterium bovis/growth & development , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/growth & development , Neural Cell Adhesion Molecules/pharmacologyABSTRACT
We describe here the capacity of human recombinant interleukin-1-beta (IL-1beta), interferon-gamma (INF-gamma), interferon-alpha (INF-alpha), tumor necrosis factor-alpha (INF-alpha), interleukin-6 (IL-6) and interleukin-2 (IL-2) to modulate phagocytosis and bacterial killing by human neutrophils. IL-1beta, INF-gamma and TNF-alpha enhance phagocytosis of bacteria but do not have consistent effect on bacterial killing. In contrast, IL-6 augments bacterial killing but not phagocytosis of bacteria by neutrophils. INF-alpha augments and IL-2 depresses both antibacterial reactions of neutrophils. A direct effect of TNF-alpha (inhibition) and IL-2 (promotion) upon bacterial growth has been observed. It is concluded that (a) phagocytosis and intracellular bacterial killing are independent reactions of neutrophil-mediated antibacterial defence on the basis of different patterns of up- and down-regulation by cytokines, and (b) cytokines can exhibit direct effects on bacterial growth.
