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Defective Fc-mediated phagocytosis in C3H/HeJ macrophages. II. Correction by cAMP agonists
Abstract:
Peritoneal macrophages from LPS hyporesponsive C3H/HeJ mice lose the capacity to bind and phagocytose opsonized sheep erythrocytes (EA) over a 48-hr culture period. This loss in Fc receptor capacity is markedly different from the progressive increase in phagocytic ability exhibited by cultured macrophages derived from LPS-responsive C3H/HeN mice. Since dibutyryl-cyclic adenosine monophosphate (DBcAMP) has previously been reported to modulate membrane receptor expression in lymphocytes and certain macrophage-like cell lines, we examined its effects on EA binding and phagocytosis by C3H/HeJ macrophages. DBcAMP not only reverses the binding defect in C3H/HeJ macrophages but also restores EA phagocytosis to the level of control C3H/HeN cultures. 8-Bromo-cAMP, as well as other agents known to elevate intracellular cAMP (i.e., isoproterenol plus isobutylmethylxanthine or prostaglandin E2) also corrected the phagocytic defect. Since the C3H/HeJ macrophage phagocytic defect can also be reversed by in vitro stimulation with a lymphokine-rich culture supernatant, we examined the effect of this treatment on intracellular cAMP levels. Lymphokine treatment produced a 60% increase in the levels of macrophage intracellular cAMP. These findings suggest that the C3H/HeJ differentiation defect may be secondary to some abnormality in a cAMP dependent pathway.
Insights
Cultured macrophages from LPS-hyporesponsive mice show reduced function. Cyclic adenosine monophosphate (cAMP) and lymphokines restore macrophage phagocytosis, suggesting a cAMP-dependent pathway defect.
Area of Science:
- Immunology
- Cell Biology
Background:
- Peritoneal macrophages from LPS-hyporesponsive C3H/HeJ mice exhibit a progressive loss in binding and phagocytosis of opsonized sheep erythrocytes (EA) over 48 hours.
- This Fc receptor-mediated function decline contrasts with the enhanced phagocytic ability seen in macrophages from LPS-responsive C3H/HeN mice.
Purpose of the Study:
- To investigate the role of cyclic adenosine monophosphate (cAMP) in the phagocytic defect of C3H/HeJ macrophages.
- To determine if modulating intracellular cAMP levels can restore Fc receptor-mediated phagocytosis.
Main Methods:
- Macrophages from C3H/HeJ mice were cultured and treated with dibutyryl-cyclic adenosine monophosphate (DBcAMP) and other cAMP-elevating agents.
- Phagocytosis and binding of opsonized sheep erythrocytes (EA) were assessed.
- Intracellular cAMP levels were measured following lymphokine stimulation.
Main Results:
- Dibutyryl-cyclic adenosine monophosphate (DBcAMP) treatment reversed the binding defect and restored EA phagocytosis in C3H/HeJ macrophages to levels comparable to C3H/HeN controls.
- Other cAMP-elevating agents, including 8-Bromo-cAMP, isoproterenol with isobutylmethylxanthine, and prostaglandin E2, also corrected the phagocytic defect.
- Lymphokine stimulation of C3H/HeJ macrophages resulted in a 60% increase in intracellular cAMP levels.
Conclusions:
- The phagocytic defect in C3H/HeJ macrophages is reversible with agents that increase intracellular cAMP.
- Lymphokine-induced reversal of the defect is associated with elevated cAMP levels.
- These findings suggest that an abnormality in a cAMP-dependent pathway may underlie the C3H/HeJ macrophage differentiation defect.