Peripheral blood mononuclear leukocytes release a mediator(s) that induces phagocytosis of C-reactive protein-coated cells by polymorphonuclear leukocytes

Abstract

We studied the phagocytosis by human polymorphonuclear leukocytes (PMN) of sheep erythrocytes (E) passively sensitized with pneumococcal C-polysaccharide (E-PnC), E-PnC coated with C-reactive protein (E-PnC-CRP), and E coated with rabbit antisheep E IgG (E-IgG). PMN isolated from the blood of normal individuals failed to ingest either E-PnC or E-PnC-CRP; however, after incubation with supernatants from stimulated peripheral blood mononuclear leukocytes, glass-adherent PMN ingested E-PnC-CRP with a mean phagocytic index of 47.8 +/- 14.9 (means +/- SD, n = 9) and E-PnC to a lesser extent with a phagocytic index of 9.6 +/- 2.9 (mean +/- SD, n = 4). We also observed a statistically significant increase in the ingestion of E-IgG by lymphokine-stimulated PMN with phagocytic indices of 85.2 +/- 21.2 (mean +/- SD, n = 12) for unstimulated PMN and 158 +/- 37.1 (mean +/- SD, n = 9) for stimulated PMN. The best conditions for stimulating release of this phagocytosis-promoting mediator included exposure to phytohemagglutinin (PHA) in the presence of monocytes that had ingested IgG-coated sheep erythrocytes. The induction of phagocytosis of E-PnC-CRP was rapid, reaching a maximal level after stimulation of the adherent PMN with the conditioned media for 30 min. The factor(s) responsible for the induction of the ingestion of E-PnC-CRP was less than 10,000 daltons and was heat stable (56 degrees C for 45 min). These data are similar to earlier results obtained with PMN activated by 12-0-tetradecanoyl-phorbol-13-acetate (PMA), an important contrast being that in the current studies PMN were activated by a soluble factor released from stimulated mononuclear cells under conditions simulating those in vivo.