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, Volume 4, Issue 4, pp 241–258 | Cite as

Regulation of lysosomal enzyme secretion: Role in inflammation

  • Louis J. Ignarro
Immunosuppression and Inflammation Reviews

Abstract

The purpose of this review is first to discuss the lysosomal concept as it applies to the mediation of tissue injury, and second to provide new evidence for the regulation of lysosomal enzyme secretion from human neutrophils by cyclic nucleotides, autonomic neurohormones, prostaglandins, glucocorticosteroids and calcium. Lysosomal enzymes gain access to the extracellular environment by the selective secretion of lysosome granule contents from neutrophils during cell contact with various immune reactants. Discharge of lysosomal contents results in the provocation of acute inflammation and connective tissue degradation. The immunologic secretion of lysosomal enzymes from human neutrophils requires the presence of extracellular calcium and can be modulated by several different classes of hormones, drugs and other agents. Agents that enhance lysosomal enzyme secretion also produce a concomitant accumulation of cyclic GMP (guanosine 3′, 5′-monophosphate) in neutrophils. Such substances include immune reactants, acetylcholine, prostaglandin F and calcium ionophores. Cyclic GMP itself also stimulates lysosomal enzyme secretion. On the other hand, inhibition of enzyme release is frequently accompanied by the accumulation of intracellular cyclic AMP (adenosine 3′, 5′-monophosphate). These effects are produced by epinephrine (catecholamines) and several prostaglandins. Cyclic AMP also inhibits lysosomal enzyme secretion. Glucocorticosteroids also inhibit enzyme secretion but this effect is accompanied by an inhibition of cyclic AMP accumulation rather than by the stimulation of cyclic AMP accumulation. The presence of cyclic GMP, cyclic AMP and the cellular processes for accumulating either nucleotide provide the human neutrophil with the means by which to modulate the secretion of lysosomal contents in response of the cells to various endogenous substances and drugs.

Keywords

Prostaglandin Monophosphate Lysosomal Enzyme Human Neutrophil Cyclic Nucleotide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Birkhäuser Verlag 1974

Authors and Affiliations

  • Louis J. Ignarro
    • 1
  1. 1.Department of PharmacologyTulane University School of MedicineNew OrleansUSA

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