Inhibition of swine microglial cell phagocytosis of Cryptococcus neoformans by femtomolar concentrations of morphine

Grzegorz Sowa, Genya Gekker, Myriam M. Lipovsky, Shuxian Hu, Chun C. Chao, Thomas W Molitor, Phillip K. Peterson

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Microglia are important immune effector cells within the brain. The phagocytosis of nonopsonized Cryptococcus neoformans by swine microglia was used as an in vitro model for studies on cellular mechanisms of opiate-mediated immunomodulation in the brain. Morphine inhibited potently (IC50 ~10-16 M) the phagocytosis of C. neoformans by primaty cultures of neonatal pig microglia. The μ opioid agonist Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol (DAMGO) also suppressed phagocytosis but with a much lower potency than morphine (IC50 ~ 10-8 M). The inhibitory effects of morphine and DAMGO were blocked by equimolar concentrations of naloxone and by the selective μ opiate receptor antagonist β-funaltrexamine. Pertussis toxin but not cholera toxin reversed the inhibitory effects of both morphine and DAMGO. Our data suggest that morphine inhibits phagocytosis of C. neoformans by swine microglia via a mechanism involving μ opiate receptors coupled to a pertussis toxin-sensitive G(i)/G(o) protein signaling pathway.

Original languageEnglish (US)
Pages (from-to)823-828
Number of pages6
JournalBiochemical Pharmacology
Volume53
Issue number6
DOIs
StatePublished - Mar 21 1997

Bibliographical note

Funding Information:
This work was supportedi,n part, by National Instituteso f He& Grants DA-04351 and DA-08446.

Keywords

  • Cryptococcus neoformans
  • microglia
  • morphine
  • phagocytosis
  • μ opiate receptor

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