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Secretion and function of the third component of complement (C3) by murine leukocytes
1Department of Immunology, Tohoku University, Sendai, Japan.
International Immunology
|June 1, 1992
Summary
Macrophages and neutrophils (PMN) synthesize and secrete complement C3. Macrophages secrete C3 constitutively, while PMN store and release C3 upon stimulation, demonstrating its opsonizing activity.
Area of Science:
- Immunology
- Cell Biology
Background:
- Complement component 3 (C3) is crucial for innate and adaptive immunity.
- The cellular sources and secretion mechanisms of C3, particularly from myeloid cells, require further elucidation.
Purpose of the Study:
- To investigate the de novo synthesis and secretion of C3 by murine peritoneal macrophages and polymorphonuclear leukocytes (PMN).
- To compare the distinct C3 secretion pathways employed by macrophages and PMN.
- To characterize the functional activity of C3 secreted by PMN.
Main Methods:
- Confirmation of C3 synthesis and secretion via [35S]methionine incorporation and cycloheximide inhibition.
- Quantification of C3 in cell culture supernatants to compare secretion modes.
- Stimulation of PMN C3 secretion using protein kinase C (PKC) activators and calcium ionophore.
- Development of a sensitive C3 activity assay.
Main Results:
- Both macrophages and PMN synthesize C3.
- Macrophages exhibit constitutive C3 secretion, whereas PMN store and release C3 in response to stimuli like PKC activators and calcium ionophore.
- A novel, sensitive assay demonstrated that PMN-secreted C3 possesses opsonizing activity, enhancing phagocytosis.
Conclusions:
- Macrophages and PMN are significant sources of C3, utilizing different secretion strategies.
- PMN C3 secretion involves PKC and calmodulin pathways.
- PMN-derived C3 actively participates in immune responses through opsonization and phagocytosis enhancement.