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Macrophage procoagulant-inducing factor. In vivo properties and chemotactic activity for phagocytic cells
Abstract:
Murine macrophage procoagulant-inducing factor (MPIF) is a lymphokine with chemical properties distinct from a number of well-characterized cytokines. MPIF induces procoagulant activity on the surface of macrophages and thus may play a central role in the expression of cell-mediated immunity. Highly enriched MPIF-alpha and -beta, separated by virtue of their basic isoelectric point and affinity for heparin, induced local induration and fibrin deposition and cellular infiltration similar to that observed in delayed type hypersensitivity reactions, when injected intradermally. Margination with of polymorphonuclear leukocytes (PMN) along the endothelium as well as increased PMN infiltration was evident after 4 h. In contrast to other inflammatory mediators (e.g., C5a, IL-1) reactivity was sustained, with greater numbers of mononuclear cells apparent 24 h after skin testing. Changes in the dermis were evident 4 h after MPIF injection with increased numbers of cells near areas where spaces in the collagen bundles had formed. Dermal thickening was evident after 24 h and collagen fiber structure was disrupted. Extravascular fibrinogen/fibrin was most prominent 24 h after testing. LPS, which induces macrophage procoagulant activity in vitro, did not induce the histopathologic changes evident with MPIF. MPIF was chemotactic for PMN and macrophages in vitro. Chemotactic activity was heat-labile and not due to C5a. Migration was dependent on a concentration gradient, as determined by checkerboard analysis, indicating that MPIF promoted chemotaxis rather than chemokinesis. Experiments reported here suggest that MPIF is an important mediator of fibrin deposition and cellular infiltration characteristic of cell-mediated immune response.
Insights
Murine macrophage procoagulant-inducing factor (MPIF) is a lymphokine that promotes fibrin deposition and cellular infiltration in immune responses. MPIF induces significant histopathologic changes, distinct from LPS, and exhibits chemotactic properties for immune cells.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Murine macrophage procoagulant-inducing factor (MPIF) is a lymphokine.
- MPIF has distinct chemical properties compared to known cytokines.
- MPIF induces procoagulant activity on macrophages, suggesting a role in cell-mediated immunity.
Purpose of the Study:
- To investigate the in vivo effects of MPIF.
- To characterize the inflammatory and histopathologic changes induced by MPIF.
- To determine the chemotactic properties of MPIF for immune cells.
Main Methods:
- Intradermal injection of purified MPIF-alpha and -beta in mice.
- Histopathologic examination of skin tissue at 4 and 24 hours post-injection.
- In vitro chemotaxis assays for polymorphonuclear leukocytes (PMN) and macrophages.
Main Results:
- MPIF induced local induration, fibrin deposition, and cellular infiltration resembling delayed type hypersensitivity reactions.
- Increased PMN margination and infiltration were observed within 4 hours.
- Sustained mononuclear cell infiltration and dermal changes, including collagen disruption and thickening, were evident at 24 hours.
- MPIF demonstrated heat-labile, dose-dependent chemotactic activity for PMN and macrophages in vitro, distinct from C5a.
- Lipopolysaccharide (LPS) did not induce similar histopathologic changes.
Conclusions:
- MPIF is a significant mediator of fibrin deposition and cellular infiltration characteristic of cell-mediated immune responses.
- MPIF exhibits potent inflammatory and chemotactic properties.
- MPIF's distinct effects differentiate it from other inflammatory mediators like LPS, C5a, and IL-1.