Mechanism of Pneumocystis carinii attachment to cultured rat alveolar macrophages

J Clin Invest. 1990 Nov;86(5):1678-83. doi: 10.1172/JCI114891.

Abstract

Pneumocystis carinii (PC) pneumonia begins as an intra-alveolar process resulting in injury to the alveolar epithelium with subsequent invasion of the lung interstitium. The clearance of PC organisms from the alveolar space is a critical function of alveolar macrophages (AM), the resident alveolar phagocytic cells. In this study the mechanism of PC attachment to AM was determined using 51Cr-labeled organisms, with PC attachment reaching a maximum of 18.9 +/- 2.5% after 4 h. Attachment was significantly decreased by preincubation of the AM with a monoclonal anti-fibronectin antibody directed against the cell attachment site of fibronectin (from 17.8 +/- 2.2% to 8.3 +/- 1.0%, P less than 0.01), or by addition of the fibronectin cell binding site analogue Arg-Gly-Asp-Ser (RGDS) (from 18.1 +/- 2.3% to 2.9 +/- 0.8%, P less than 0.01). An anti-fibronectin monoclonal antibody directed against the heparin binding domain of fibronectin had no effect on PC attachment. Addition of the specific calcium ion chelating agent EGTA to the culture media similarly decreased attachment from 16.9 +/- 2.0% to 5.1 +/- 1.1% (P less than 0.01). Fibronectin-mediated attachment of PC to AM did not result in phagocytosis of the organisms by the AM as determined by chemiluminescence measurements. Therefore, the data indicate that PC attachment to AM is a calcium-dependent process mediated by the cell binding domain of fibronectin which does not trigger a phagocytic response by the AM.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal
  • Binding Sites
  • Cells, Cultured
  • Egtazic Acid
  • Fibronectins / immunology
  • Fibronectins / metabolism
  • Heparin / metabolism
  • Kinetics
  • Macrophages / immunology
  • Macrophages / microbiology*
  • Molecular Sequence Data
  • Oligopeptides / pharmacology
  • Phagocytosis
  • Pneumocystis / immunology
  • Pneumocystis / metabolism*
  • Pulmonary Alveoli
  • Rats
  • Rats, Inbred Strains

Substances

  • Antibodies, Monoclonal
  • Fibronectins
  • Oligopeptides
  • Egtazic Acid
  • Heparin
  • arginyl-glycyl-aspartyl-serine