Murine laminin binds to Histoplasma capsulatum. A possible mechanism of dissemination

J Clin Invest. 1995 Aug;96(2):1010-7. doi: 10.1172/JCI118086.

Abstract

Histoplasmosis, an increasingly important opportunistic infection in immunosuppressed subjects, is characterized by hematogenous dissemination of the yeast from the lung. The mechanism of this dissemination is not fully understood. Laminin, the major glycoprotein of the extracellular matrix, is known to mediate the attachment of various invasive pathogens to host tissues. In the current study, laminin is demonstrated to bind to Histoplasma capsulatum in a rapid, specific, and saturable manner. Scatchard analysis with 125I-labeled laminin revealed an estimated 3.0 x 10(4) binding sites per yeast with an apparent Kd for laminin binding of 1.6 x 10(-9) M. Laminin binding to H. capsulatum was decreased from 62 +/- 1 to 17 +/- 1 ng (P < 0.001) in the presence of 3,000 nM of Ile-Lys-Val-Ala-Val, a pentapeptide within one major cell attachment site of laminin. A 50-kD H. capsulatum laminin-binding protein was demonstrated using an 125I-Ln blot of H. capsulatum cell wall proteins. The 50-kD protein is also recognized by antibodies directed at the 67-kD laminin receptor, suggesting they are related. This study proposes a possible mechanism for H. capsulatum attachment to laminin, an important first step required for the yeast to recognize and traverse the basement membrane.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Amino Sugars / pharmacology
  • Animals
  • Antibodies, Fungal / immunology
  • Antibodies, Fungal / pharmacology
  • Basement Membrane / metabolism
  • CD4-Positive T-Lymphocytes
  • Cell Adhesion / drug effects
  • Cell Wall / metabolism
  • Fungal Proteins / immunology
  • Fungal Proteins / metabolism
  • Histoplasma / immunology
  • Histoplasma / metabolism*
  • Histoplasma / pathogenicity
  • Laminin / chemistry
  • Laminin / metabolism*
  • Laminin / pharmacology
  • Lymphocyte Depletion
  • Macrophages / microbiology
  • Membrane Proteins / metabolism
  • Methylmannosides / pharmacology
  • Mice
  • Molecular Sequence Data
  • Oligopeptides / metabolism
  • Oligopeptides / pharmacology
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology
  • Protein Binding / drug effects

Substances

  • 50-kDa protein, Ajellomyces capsulatus
  • Amino Sugars
  • Antibodies, Fungal
  • Fungal Proteins
  • Laminin
  • Membrane Proteins
  • Methylmannosides
  • Oligopeptides
  • Peptide Fragments
  • tyrosyl-isoleucyl-glycyl-seryl-arginine
  • isoleucyl-lysyl-valyl-alanyl-valine
  • N-acetyllactosamine
  • methylmannoside