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Published on: December 26, 2013
Action and target cell specificity of human macrophage-stimulating protein (MSP)
1Immunopathology Section, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702.
Abstract:
Macrophage-stimulating protein (MSP) induces mouse resident peritoneal macrophages to become responsive to the chemoattractant C5a and to ingest C3bi-coated erythrocytes. We now show that MSP action is not limited to complement-induced responses, because it also induced responsiveness to the noncomplement chemoattractant casein. In addition to stimulating responsiveness to attractants, MSP functioned alone as a chemoattractant for resident peritoneal macrophages, with an optimal concentration of approximately 0.2 nM. A critical difference between MSP and C5a is that resident macrophages did not migrate to C5a without an additional stimulus such as MSP in the cell suspension, whereas macrophages suspended in medium alone migrated to MSP in the attractant well. Thus, in contrast to C5a, MSP seems capable of a dual role, both activator and attractant. MSP had no effect on responsiveness of mouse peritoneal exudate macrophages to C5a; nor could it attract exudate macrophages or human blood monocytes. Absorption studies showed that resident macrophages have a receptor for MSP, but exudate macrophages do not. In view of these findings, it seems that the biological role of MSP is not as a recruiter of blood monocytes to sites of inflammation, but as an activator of mature macrophages. The MSP-induced activated state for responsiveness to C5a or C3bi was transient, and decayed at a first order rate with a t 1/2 of approximately 1 h. This is a new example of the transience of activation induced in macrophages by proinflammatory stimuli.
Insights
Macrophage-stimulating protein (MSP) activates macrophages and attracts them to sites of inflammation. This activation is transient, highlighting a new aspect of inflammatory responses.
Area of Science:
- Immunology
- Cell Biology
Background:
- Macrophage-stimulating protein (MSP) is known to prime macrophages for responses to chemoattractants like C5a and enhance phagocytosis.
- The precise roles and mechanisms of MSP in macrophage activation and migration remain incompletely understood.
Purpose of the Study:
- To investigate the dual role of MSP as both an activator and chemoattractant for macrophages.
- To determine the specificity of MSP action on different macrophage populations and its effect on inflammatory responses.
Main Methods:
- Utilized mouse resident peritoneal macrophages and exudate macrophages, along with human blood monocytes.
- Assessed macrophage responsiveness to MSP and other chemoattractants (C5a, casein) using migration assays.
- Employed absorption studies to identify MSP receptors on macrophages.
Main Results:
- MSP acts as a chemoattractant for resident macrophages at optimal concentrations (~0.2 nM) and induces responsiveness to non-complement attractants like casein.
- Unlike C5a, MSP can independently induce macrophage migration, suggesting a dual activator and attractant role.
- Resident macrophages possess MSP receptors, while exudate macrophages and human monocytes do not, indicating specificity in MSP action.
- The MSP-induced activation state is transient, decaying with a half-life of approximately 1 hour.
Conclusions:
- MSP functions primarily as an activator of mature macrophages rather than a recruiter of blood monocytes to inflammatory sites.
- The transient nature of MSP-induced activation provides a novel example of temporary activation by pro-inflammatory stimuli.
- These findings elucidate the specific roles of MSP in modulating macrophage behavior during inflammatory processes.
