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Peripheral blood mononuclear leukocytes release a mediator(s) that induces phagocytosis of C-reactive protein-coated
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.
Insights
Human polymorphonuclear leukocytes (PMN) showed enhanced phagocytosis of opsonized sheep erythrocytes after stimulation with soluble factors from activated mononuclear cells. This study reveals a novel pathway for PMN activation in immune responses.
Area of Science:
- Immunology
- Cell Biology
Background:
- Human polymorphonuclear leukocytes (PMN) are crucial immune cells involved in pathogen clearance.
- Phagocytosis, the process by which cells engulf particles, is a key function of PMN.
- Understanding PMN activation is vital for developing strategies against infections and inflammatory diseases.
Purpose of the Study:
- To investigate the phagocytic activity of human PMN against opsonized sheep erythrocytes (E).
- To determine if supernatants from stimulated peripheral blood mononuclear leukocytes can enhance PMN phagocytosis.
- To characterize the nature of the phagocytosis-promoting factor(s).
Main Methods:
- Human PMN were isolated and incubated with sheep erythrocytes sensitized with pneumococcal C-polysaccharide (E-PnC), E-PnC with C-reactive protein (E-PnC-CRP), or E coated with IgG (E-IgG).
- PMN phagocytosis was assessed after incubation with supernatants from stimulated peripheral blood mononuclear leukocytes.
- Phagocytic indices were measured, and the characteristics (size, heat stability) of the active factor were determined.
Main Results:
- Unstimulated PMN showed limited ingestion of E-PnC and E-PnC-CRP.
- Supernatants from stimulated mononuclear leukocytes significantly enhanced PMN phagocytosis of E-PnC-CRP (index 47.8) and E-IgG (index 158).
- The phagocytosis-promoting factor was <10,000 daltons and heat-stable, released rapidly upon stimulation.
Conclusions:
- Soluble factors released from stimulated mononuclear cells can potently activate human PMN for enhanced phagocytosis.
- This activation pathway, mediated by a heat-stable, low-molecular-weight factor, offers a novel mechanism for immune cell recruitment and function.
- The findings provide insights into PMN activation under conditions mimicking in vivo immune responses.