Evidence for Pneumocystis carinii binding to a cell-free substrate: role of the adhesive protein fibronectin.
Attachment of Pneumocystis carinii organisms to the alveolar epithelium is probably a prerequisite for the initiation of P. carinii infection. Previous studies have demonstrated a role for the extracellular matrix protein fibronectin in mediating attachment of P. carinii organisms to cultured alveolar cells; however, these studies could not clearly distinguish the role of fibronectin binding to P. carinii organisms and fibronectin binding to the alveolar cells. The current study demonstrates the direct binding of P. carinii organisms to substrate-bound soluble fibronectin P. carinii organisms bound specifically in a concentration-dependent manner to fibronectin-coated plates; maximum binding (19.1% +/- 1.9%) occurred at a fibronectin concentration of 50 micrograms/ml. P. carinii organisms did not bind significantly to bovine serum albumin-coated plates (5.8% +/- 1.2%). Binding of P. carinii organisms to fibronectin-coated plates was inhibited in a concentration-dependent manner by addition of the tetrapeptide arginine-glycine-aspartic acid-serine, which represents the active site of the fibronectin cell-binding domain. Similarly, attachment of P. carinii organisms was significantly inhibited by the addition of monoclonal antibodies directed against the cell-binding domain of fibronectin or by the addition of calcium ion chelators. To evaluate the role of the major P. carinii surface antigen gp120 in attachment of P. carinii organisms, purified gp120 and specific polyclonal anti-gp120 antibodies were used to inhibit attachment of P. carinii organisms to fibronectin-coated plates.(ABSTRACT TRUNCATED AT 250 WORDS)
Pottratz
S T
ST
Department of Internal Medicine, Indiana University School of Medicine, Indianapolis.
Paulsrud
J R
JR
Smith
J S
JS
Martin
W J
WJ
D001665:Binding Sites; D002118:Calcium / Q000494:pharmacology; D002448:Cell Adhesion / Q000502:physiology*; D002478:Cells, Cultured; D004533:Egtazic Acid / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000502:physiology; D009842:Oligopeptides / Q000378:metabolism; D011010:Pneumocystis / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000382:microbiology*
D005353:Fibronectins; D008562:Membrane Glycoproteins; D009842:Oligopeptides; D004533:Egtazic Acid; C047981:arginyl-glycyl-aspartic acid; D006493:Heparin; D002118:Calcium