Secretion of plasminogen activator by human polymorphonuclear leukocytes. Modulation by glucocorticoids and other

Insights

Human neutrophils (PMNs) secrete plasminogen activator, a process regulated by inflammation-affecting agents and distinct from other lytic enzyme release, suggesting a role in cell migration.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Human polymorphonuclear neutrophils (PMNs) are key immune cells involved in inflammatory responses.
  • The secretion of specific enzymes by PMNs plays a crucial role in their function and interaction with tissues.
  • Plasminogen activator is an enzyme secreted by various cells, involved in fibrinolysis and extracellular matrix remodeling.

Purpose of the Study:

  • To investigate the regulation of plasminogen activator secretion by human PMNs.
  • To compare the regulatory mechanisms of plasminogen activator production with those of other granule-bound enzymes, such as elastase.
  • To explore the potential role of plasminogen activator secretion in PMN inflammatory responses and cell migration.

Main Methods:

  • Purification of human PMNs.
  • Stimulation of PMN secretion using Concanavalin A (Con A) and phorbol 12-myristate 13-acetate (PMA) at varying concentrations.
  • Inhibition studies using glucocorticoids, cyclic adenosine monophosphate (cAMP), actinomycin D, and cycloheximide.
  • Assay of plasminogen activator and elastase release.

Main Results:

  • Plasminogen activator secretion by PMNs is stimulated by Con A and low concentrations of PMA.
  • Glucocorticoids, cAMP, actinomycin D, and cycloheximide inhibit plasminogen activator production.
  • Release of granule-bound elastase requires higher PMA concentrations and is unaffected by the inhibitors that block plasminogen activator production.

Conclusions:

  • PMN plasminogen activator production is distinctly regulated by agents influencing inflammation, separate from other lytic enzymes like elastase.
  • The specific control mechanisms suggest a unique role for plasminogen activator in the PMN response pattern.
  • Findings support the hypothesis that plasminogen activator secretion correlates with cell migration in vivo, similar to observations in macrophages.

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