MURINE LAMININ BINDS TO HISTOPLASMA-CAPSULATUM - A POSSIBLE MECHANISMOF DISSEMINATION

Histoplasmosis, an increasingly important opportunistic infection in i mmunosuppressed subjects, is characterized by hematogenous disseminati on of the yeast from the lung. The mechanism of this dissemination is not fully understood. Laminin, the major glycoprotein of the extracell ular matrix, is known to mediate the attachment of various invasive pa thogens 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 I-125-labeled laminin revealed an est imated 3.0 x 10(4) binding sites per yeast with an apparent K-d for la minin 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 3,00 0 nM of Ile-Lys-Val-Ala-Val, a pentapeptide within one major cell atta chment site of laminin, A. 50-kD H, capsulatum laminin-binding protein was demonstrated using an I-125-Ln blot of H. capsulatum cell wall pr oteins, The 50-kD protein is also recognized by antibodies directed at the 67-kD laminin receptor, suggesting they are related, This study p roposes a possible mechanism for H. capsulatum attachment to laminin, an important first step required for the yeast to recognize and traver se the basement membrane.