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Mechanisms of lysosomal enzyme release from leukocytes exposed to immune complexes and other particles

G Weissmann1, R B Zurier, P J Spieler

  • 1Department of Medicine, New York University School of Medicine, New York 10016.

The Journal of Experimental Medicine
|October 30, 2009
PubMed

Insights

Human white blood cells (PMN) selectively release lysosomal enzymes when encountering immune complexes, without cell death. This process, crucial for immune responses, can be modulated by intracellular signaling molecules.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Human neutrophils (PMN) are key immune cells involved in pathogen clearance.
  • Lysosomal enzymes play critical roles in cellular defense and tissue remodeling.
  • Immune complex recognition triggers various cellular responses in PMN.

Purpose of the Study:

  • To investigate the specific release of lysosomal enzymes from human PMN upon exposure to immune complexes.
  • To differentiate this release mechanism from general cell death-induced enzyme leakage.
  • To explore factors influencing and modulating this selective enzyme release.

Main Methods:

  • Exposure of human PMN to immune complexes, zymosan, and MSU crystals.
  • Measurement of lysosomal enzymes (beta-glucuronidase, acid phosphatase) and cytoplasmic LDH in supernatants.
  • Assessment of cell viability.
  • Investigation of the effects of serum, Tris buffer, and cAMP-elevating agents (PGE(1), theophylline, 2-CA).

Main Results:

  • Human PMN selectively released lysosomal enzymes upon encountering immune complexes and zymosan, without releasing cytoplasmic LDH, indicating cell viability.
  • This selective release mechanism is distinct from cell death-induced enzyme release caused by MSU crystals.
  • The process was not significantly affected by platelet contamination or serum, but was inhibited by agents that increase intracellular cAMP levels.
  • Uptake of particles correlated with increased glucose oxidation.

Conclusions:

  • Human PMN selectively extrude lysosomal hydrolases during phagocytosis of immune complexes and zymosan, a process distinct from cell lysis.
  • This regulated release mechanism is independent of Tris buffer but can be inhibited by elevated intracellular cAMP.
  • Leukocyte response to immune particles involves a controlled regurgitation of lysosomal contents, contributing to immune regulation.

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