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Platelet-derived growth factor promotes human peripheral monocyte activation
Abstract:
Like in the polymorphonuclear leukocyte (PMN), the platelet-derived growth factor (PDGF) purified to homogeneity is capable of inducing monocyte activation responses as evaluated by generation of superoxide anion (O-.2) from membrane-associated oxidase system, release of granule enzymes, and enhanced cell adherence and cell aggregation. Superoxide anion release was maximized at 10 ng/mL PDGF and was comparable to that induced by 10(-7) mol/L formyl-methionyl-leucyl-phenylalanine. The potency of PDGF to induce this response in monocytes was of the same magnitude as that observed in PMNs. Similarly, lysozyme release and monocyte adherence were also increased in a dose-dependent manner and achieved maximal responses at 40 ng/mL concentration of PDGF. The PDGF concentration required to achieve maximal monocyte aggregation was two-fold (60 ng/mL) of that found for PMNs. In contrast to PMNs, a positive correlation (gamma = .93; P less than .01) was observed between the increases of PDGF concentration and beta-glucuronidase release. These findings indicate that PDGF can induce the full sequence of cell activation events in human monocytes similar to human PMNs.
Insights
Platelet-derived growth factor (PDGF) activates human monocytes similarly to polymorphonuclear leukocytes (PMNs). PDGF induces superoxide anion generation, enzyme release, and cell adherence, demonstrating its role in monocyte activation.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Platelet-derived growth factor (PDGF) is a potent mitogen and chemoattractant.
- Polymorphonuclear leukocytes (PMNs) are key immune cells involved in inflammatory responses.
- Monocytes play crucial roles in innate and adaptive immunity, differentiating into macrophages and dendritic cells.
Purpose of the Study:
- To investigate the effects of purified platelet-derived growth factor (PDGF) on human monocyte activation.
- To compare the activation responses of monocytes induced by PDGF with those induced by formyl-methionyl-leucyl-phenylalanine (fMLP) and with responses in PMNs.
Main Methods:
- Purification of PDGF to homogeneity.
- Assay of superoxide anion (O-.2) generation using a membrane-associated oxidase system.
- Measurement of granule enzyme release (lysozyme, beta-glucuronidase).
- Evaluation of cell adherence and cell aggregation.
- Dose-response studies with varying PDGF concentrations.
Main Results:
- PDGF induced superoxide anion generation, lysozyme release, and enhanced cell adherence and aggregation in monocytes.
- Superoxide anion release was maximized at 10 ng/mL PDGF, comparable to fMLP.
- Lysozyme release and monocyte adherence increased dose-dependently, with maximal responses at 40 ng/mL PDGF.
- Monocyte aggregation required a higher PDGF concentration (60 ng/mL) compared to PMNs.
- A positive correlation was observed between PDGF concentration and beta-glucuronidase release in monocytes.
Conclusions:
- PDGF induces a comprehensive set of activation events in human monocytes.
- The activation profile of monocytes by PDGF closely resembles that observed in PMNs.
- PDGF is a significant factor in modulating monocyte inflammatory and immune functions.