Surfactant protein D-mediated aggregation of Pneumocystis carinii impairs phagocytosis by alveolar macrophages

Suk Joong Yong, Zvezdana Vuk-Pavlovic, Joseph E. Standing, Erika C. Crouch, Andrew Harold Limper

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Pneumocystis carinii remains an important and potentially fatal cause of opportunistic pneumonia. Animal studies reveal that substantial quantities of surfactant protein D (SP-D) accumulate in the airspaces during P. carinii pneumonia and are particularly abundant in aggregates of organisms. Due to the multimeric structure of SP-D, we hypothesized that SP-D mediates aggregation of the organism. From previous clinical studies it is known that aggregated organisms are conspicuous in sections of lung tissue and bronchoalveolar lavage (BAL) fluids of humans with active P. carinii pneumonia. Herein, we observe that SP-D levels increased at least fourfold in BAL fluids of patients with P. carinii pneumonia. Next, a spectrophotometric sedimentation assay was developed to assess the aggregation of P. carinii in vitro by SP-D. P. carinii organisms were first stripped with glutathione to remove bound SP-D and subsequently incubated in the presence of SP-D and 2 mM calcium. P. carinii incubated with natural SP-D (10 μg/ml) containing dodecamers and higher-order forms exhibited aggregation and enhanced sedimentation compared to that of glutathione-stripped P. carinii. Aggregation was also enhanced by the concentrated supernatant of rat BAL fluid, and this effect was abolished by the selective removal of SP-D from the lavage fluid. P. carinii aggregation was reduced by maltose, mannose, and EDTA, consistent with the role of the SP-D C-type lectin domain (CRD) in the aggregation event. Comparisons of different molecular forms of SP-D showed that dodecamers - but not trimeric subunits - mediate optimal aggregation of P. carinii. Aggregation of P. carinii by SP-D was shown to be responsible for the impaired phagocytosis of the organisms by alveolar macrophages. Thus, SP-D-mediated aggregation of P. carinii may represent one means by which the organism avoids elimination by the host.

Original languageEnglish (US)
Pages (from-to)1662-1671
Number of pages10
JournalInfection and Immunity
Volume71
Issue number4
DOIs
StatePublished - Apr 1 2003

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Pulmonary Surfactant-Associated Protein D
Pneumocystis carinii
Alveolar Macrophages
Phagocytosis
Bronchoalveolar Lavage Fluid
Pneumocystis Pneumonia
Glutathione
Dilatation and Curettage
Maltose
Therapeutic Irrigation
Mannose
Lectins
Surface-Active Agents
Edetic Acid

ASJC Scopus subject areas

  • Immunology

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Surfactant protein D-mediated aggregation of Pneumocystis carinii impairs phagocytosis by alveolar macrophages. / Yong, Suk Joong; Vuk-Pavlovic, Zvezdana; Standing, Joseph E.; Crouch, Erika C.; Limper, Andrew Harold.

In: Infection and Immunity, Vol. 71, No. 4, 01.04.2003, p. 1662-1671.

Research output: Contribution to journalArticle

Yong, Suk Joong ; Vuk-Pavlovic, Zvezdana ; Standing, Joseph E. ; Crouch, Erika C. ; Limper, Andrew Harold. / Surfactant protein D-mediated aggregation of Pneumocystis carinii impairs phagocytosis by alveolar macrophages. In: Infection and Immunity. 2003 ; Vol. 71, No. 4. pp. 1662-1671.
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