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Gamma-interferon is the factor in lymphokine that activates human macrophages to inhibit intracellular Chlamydia
Abstract:
We have demonstrated previously that mitogen-induced lymphokines activate human monocyte-derived macrophages to inhibit the intracellular replication of Chlamydia psittaci. To identify the factor(s) in crude lymphokines responsible for this antimicrobial effect, we tested human Con A-induced lymphokines for interferon activity. We also attempted to neutralize the lymphokines with a monoclonal antibody directed against human gamma-interferon and examined the ability of partially purified human gamma-interferon to induce macrophage antichlamydial activity. The lymphokine-induced antichlamydial effect was measured by the inhibition of chlamydial inclusion formation in Giemsa-stained macrophage cultures. Our lymphokines were found to be rich in gamma-interferon; treatment of cells for 48 hr before infection with lymphokines containing 300 U/ml of interferon resulted in an 89% inhibition of chlamydial growth. This lymphokine effect was completely abolished by monoclonal antibody against human gamma-interferon, but not by antisera against human alpha- or beta-interferons. In addition, partially purified human gamma-interferon alone induced macrophages to restrict chlamydial growth by 95%. We conclude that it is the gamma-interferon present in human Con A-induced lymphokines that activates monocyte-derived macrophages to inhibit chlamydial replication.
Insights
Human gamma-interferon in lymphokines activates macrophages to fight Chlamydia psittaci. This finding identifies gamma-interferon as key to the anti-chlamydial effect in monocyte-derived macrophages.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Mitogen-induced lymphokines activate macrophages to inhibit Chlamydia psittaci replication.
- Identifying the specific lymphokine responsible for this antimicrobial activity is crucial.
Purpose of the Study:
- To determine if interferon is the factor in lymphokines that activates macrophages against Chlamydia.
- To investigate the role of human gamma-interferon in macrophage antichlamydial activity.
Main Methods:
- Testing human Con A-induced lymphokines for interferon activity.
- Neutralizing lymphokines with a monoclonal antibody against human gamma-interferon.
- Assessing the ability of partially purified human gamma-interferon to induce macrophage antichlamydial activity by measuring inhibition of chlamydial inclusion formation.
Main Results:
- Human lymphokines were rich in gamma-interferon, inhibiting chlamydial growth by 89% at 300 U/ml.
- The lymphokine's antichlamydial effect was abolished by anti-gamma-interferon antibody but not by anti-alpha or anti-beta interferon antisera.
- Partially purified human gamma-interferon alone induced a 95% restriction of chlamydial growth in macrophages.
Conclusions:
- Human gamma-interferon in lymphokines activates monocyte-derived macrophages.
- Gamma-interferon is the primary factor responsible for inhibiting intracellular Chlamydia psittaci replication.