Pneumocystis carinii induces the release of arachidonic acid and its metabolites from alveolar macrophages.

M. Castro, Timothy Ian Morgenthaler, O. A. Hoffman, J. E. Standing, M. S. Rohrbach, Andrew Harold Limper

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Pneumocystis carinii is an opportunistic organism that causes severe lung injury in immunocompromised hosts. Macrophage responses to P. carinii are poorly defined. Arachidonic acid (AA) and its metabolites are potent mediators of inflammation and have been implicated in host response to microorganisms. We therefore examined the production of eicosanoids from rat and rabbit alveolar macrophages stimulated with purified P. carinii. [14C]AA-labeled rabbit macrophages released 8.50 +/- 1.33% of the incorporated [14C]AA after 90 min in response to P. carinii (P = 0.0001 compared with unstimulated controls). In contrast, a similar number of rat alveolar macrophages exhibited a smaller but significant response to P. carinii, releasing 3.84 +/- 1.54% of their [14C]AA after 90 min (P = 0.001 compared with control). We further determined that P. carinii stimulated substantial production of prostaglandin E2 and concurrently a small amount of leukotriene B4 release from alveolar macrophages. To further investigate whether serum opsonization of P. carinii enhances these alterations in AA metabolism, we assessed the effect of P. carinii immune serum on P. carinii-induced AA release. P. carinii opsonized with this antiserum caused significantly greater AA release from rat alveolar macrophages than either unopsonized P. carinii or organisms opsonized with nonimmune serum. Previous studies suggest that P. carinii interacts with macrophage beta-glucan and mannose receptors. However, incubation of macrophages with P. carinii in the presence of either soluble beta-glucan or alpha-mannan failed to alter the release of AA from macrophages in response to P. carinii. Macrophage release of eicosanoids represents a potentially important host inflammatory response to P. carinii infection.

Original languageEnglish (US)
Pages (from-to)73-81
Number of pages9
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume9
Issue number1
StatePublished - Jul 1993

Fingerprint

Pneumocystis carinii
Alveolar Macrophages
Metabolites
Arachidonic Acid
Macrophages
Rats
Eicosanoids
Immune Sera
Mannans
Inflammation Mediators
beta-Glucans
Leukotriene B4
Dinoprostone
Metabolism
Microorganisms
Pneumocystis Infections
Rabbits
Immunocompromised Host
Lung Injury
Serum

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Pulmonary and Respiratory Medicine

Cite this

Pneumocystis carinii induces the release of arachidonic acid and its metabolites from alveolar macrophages. / Castro, M.; Morgenthaler, Timothy Ian; Hoffman, O. A.; Standing, J. E.; Rohrbach, M. S.; Limper, Andrew Harold.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 9, No. 1, 07.1993, p. 73-81.

Research output: Contribution to journalArticle

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abstract = "Pneumocystis carinii is an opportunistic organism that causes severe lung injury in immunocompromised hosts. Macrophage responses to P. carinii are poorly defined. Arachidonic acid (AA) and its metabolites are potent mediators of inflammation and have been implicated in host response to microorganisms. We therefore examined the production of eicosanoids from rat and rabbit alveolar macrophages stimulated with purified P. carinii. [14C]AA-labeled rabbit macrophages released 8.50 +/- 1.33{\%} of the incorporated [14C]AA after 90 min in response to P. carinii (P = 0.0001 compared with unstimulated controls). In contrast, a similar number of rat alveolar macrophages exhibited a smaller but significant response to P. carinii, releasing 3.84 +/- 1.54{\%} of their [14C]AA after 90 min (P = 0.001 compared with control). We further determined that P. carinii stimulated substantial production of prostaglandin E2 and concurrently a small amount of leukotriene B4 release from alveolar macrophages. To further investigate whether serum opsonization of P. carinii enhances these alterations in AA metabolism, we assessed the effect of P. carinii immune serum on P. carinii-induced AA release. P. carinii opsonized with this antiserum caused significantly greater AA release from rat alveolar macrophages than either unopsonized P. carinii or organisms opsonized with nonimmune serum. Previous studies suggest that P. carinii interacts with macrophage beta-glucan and mannose receptors. However, incubation of macrophages with P. carinii in the presence of either soluble beta-glucan or alpha-mannan failed to alter the release of AA from macrophages in response to P. carinii. Macrophage release of eicosanoids represents a potentially important host inflammatory response to P. carinii infection.",
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