In vitro suppression of serum elastase-inhibitory capacity by reactive oxygen species generated by phagocytosing...

Area of Science:

• Biochemistry
• Immunology
• Cell Biology

Background:

• Human polymorphonuclear leukocytes (PMN) are key immune cells involved in inflammation.
• These cells release reactive oxygen species (ROS) during phagocytosis.
• Alpha1-proteinase inhibitor (alpha1-PI) is a crucial serum proteinase inhibitor that protects tissues.

Purpose of the Study:

• To investigate the role of activated oxygen species produced by PMN in suppressing the elastase-inhibiting capacity (EIC) of human serum and alpha1-PI.
• To identify the specific ROS involved in this suppressive effect.

Main Methods:

• Incubation of human serum or purified alpha1-PI with phagocytosing PMN or an artificial superoxide-generating system (xanthine/xanthine oxidase).
• Assessment of EIC using elastase-inhibiting capacity assays.
• Use of scavengers like superoxide dismutase, catalase, mannitol, and sodium azide (NaN3) to probe the involvement of specific ROS and enzymes.

Main Results:

• Activated oxygen species produced by PMN partially suppressed the EIC of serum and alpha1-PI.
• Superoxide dismutase, catalase, mannitol, and NaN3 offered partial protection, indicating the involvement of hydroxyl radical and myeloperoxidase-mediated reactions.
• An artificial system mimicking PMN superoxide production also suppressed EIC.

Conclusions:

• Stimulated PMN release potent oxidants that can inactivate alpha1-proteinase inhibitor.
• Oxidative inactivation of proteinase inhibitors by PMN-derived oxidants in inflammatory sites may lead to increased protease activity and connective tissue damage.