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Autologous neutrophils inhibit production of colony stimulating activity by normal human lymphocytes
Abstract:
Experiments were designed to study the way in which normal human polymorphs (PMNs) inhibit the production or release of colony stimulating activity (CSA) by normal lymphocytes incubated alone or in conjunction with normal monocytes. PMNs were first incubated with lymphocytes for various periods at various concentrations. The PMNs were then removed and the 'conditioned' lymphocytes were used alone or after addition to adherent mononuclear cells (monocytes) for the production of conditioned medium. The samples of conditioned medium were then assayed for CSA in a standard system for culturing granulocyte/macrophage progenitor cells (CFU-C) in agar. We found that the capacity of PMNs to inhibit CSA production by lymphocytes or by lymphocytes plus monocytes was directly proportional to the number of PMNs originally incubated and maximal at relatively short incubation times (i.e. 2-4 h). Such inhibition could be counteracted by the introduction of known stimulators of CSA production by monocytes, e.g. phytohaemagglutinin or bacterial toxin. We conclude that normal lymphocytes 'conditioned' or 'programmed' by contact with PMNs may themselves have a reduced capacity to produce CSA and may also act to reduce CSA production by monocytes. Such programmed lymphocytes could thus be a component of the mechanism by which PMNs exert a physiological inhibition on CSA-dependent granulopoiesis in vivo.
Insights
Human polymorphonuclear cells (PMNs) can inhibit colony-stimulating activity (CSA) production by lymphocytes and monocytes. This PMN-induced inhibition of CSA may play a role in regulating granulopoiesis.
Area of Science:
- Immunology
- Hematology
Background:
- Polymorphonuclear cells (PMNs) are key immune cells involved in inflammation and host defense.
- Colony-stimulating activity (CSA) is crucial for the production of granulocytes and macrophages.
- The interaction between PMNs, lymphocytes, and monocytes in regulating CSA is not fully understood.
Purpose of the Study:
- To investigate the inhibitory effect of normal human PMNs on CSA production by lymphocytes and monocytes.
- To elucidate the mechanism by which PMNs influence CSA-dependent granulopoiesis.
Main Methods:
- Human PMNs were incubated with lymphocytes for varying periods and concentrations.
- Conditioned lymphocytes were then incubated with monocytes for CSA production.
- Conditioned medium was assayed for CSA using a standard CFU-C culture system.
Main Results:
- PMN-mediated inhibition of CSA production was dose-dependent and time-dependent, with maximal inhibition observed at short incubation times (2-4 hours).
- Inhibition could be overcome by introducing known CSA stimulators like phytohaemagglutinin or bacterial toxins.
- Lymphocytes conditioned by PMNs exhibited reduced CSA production and also inhibited monocyte-derived CSA production.
Conclusions:
- Normal lymphocytes, when exposed to PMNs, can become 'programmed' to reduce CSA production.
- Programmed lymphocytes may contribute to the physiological inhibition of CSA-dependent granulopoiesis by PMNs in vivo.