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Non-chemotactic translocation of phagocytic cells mediated by a fibronectin-related human lymphokine
H P Godfrey1, D A Frenz, L S Canfield
1Department of Pathology, New York Medical College, Valhalla, 10595.
Abstract:
A fibronectin (FN)-related human lymphokine, macrophage agglutination factor (MAggF), agglutinates monocytes at femtomolar concentrations. Similar concentrations of MAggF translocate monocytes and neutrophils through artificial extracellular matrices by a non-chemotactic adhesive process not dependent on intracellular metabolism (matrix-driven translocation). As is the case with matrix-driven translocation mediated by other FN, MAggF-mediated translocation depends on interaction of the lymphokine amino-terminal heparin-binding domain with cell surface heparin-like molecules. In contrast, lymphokine-mediated agglutination involves interactions between the MAggF cell-binding domain and integrin FN receptors recognizing the Arg-Gly-Asp sequence. MAggF-mediated translocation and agglutination are also dependent on the lymphokine gelatin-binding domain. The extremely high activity of MAggF in translocating and agglutinating monocytes may result from cooperative interactions between multiple lymphokine domains and multiple classes of cell surface receptor molecules. We suggest that MAggF-mediated matrix-driven translocation could act independently of or in addition to chemotaxis in recruiting monocytes and neutrophils to a tissue site of T cell-mediated inflammation. Subsequent interaction of MAggF and monocyte FN receptor could then detain monocytes there.
Insights
Macrophage agglutination factor (MAggF) agglutinates and translocates monocytes and neutrophils via matrix-driven translocation. This lymphokine utilizes multiple domains and cell surface receptors for potent immune cell recruitment and retention.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Fibronectin (FN)-related lymphokines play roles in immune cell function.
- Macrophage agglutination factor (MAggF) is a novel lymphokine with potential immune regulatory functions.
Purpose of the Study:
- To investigate the mechanisms by which MAggF agglutinates and translocates monocytes and neutrophils.
- To elucidate the specific domains and cell surface interactions involved in MAggF activity.
Main Methods:
- Studied MAggF's effects on monocyte and neutrophil agglutination and translocation through artificial extracellular matrices.
- Investigated the role of MAggF's amino-terminal heparin-binding domain, cell-binding domain, and gelatin-binding domain.
- Examined interactions with cell surface heparin-like molecules and integrin FN receptors.
Main Results:
- MAggF agglutinates monocytes at femtomolar concentrations.
- MAggF mediates non-chemotactic, matrix-driven translocation of monocytes and neutrophils.
- MAggF-mediated processes depend on its heparin-binding, cell-binding, and gelatin-binding domains, and interactions with cell surface receptors.
Conclusions:
- MAggF exhibits potent agglutination and matrix-driven translocation activities.
- Cooperative interactions between MAggF domains and cell surface receptors likely contribute to its high efficacy.
- MAggF may recruit and retain monocytes and neutrophils at sites of inflammation, independent of or in addition to chemotaxis.