PNEUMOCYSTIS CARINII--MACROPHAGE UPTAKE AND ACTIVATION

Project: Research project

Project Details

Description

DESCRIPTION: (Adapted from the applicant's abstract and Specific Aims.)
Pneumocystis carinii is an opportunistic fungus which causes severe
pneumonia in immunocompromised hosts including patients with hematologic
and solid malignancies, organ transplantation and AIDS. P. carinii has
a complex life cycle alternating between cyst and trophozoite forms
which live on the epithelium of the lower respiratory tract. Evidence
suggests that alveolar macrophages mediate the uptake and removal of P.
carinii from alveolar spaces and serve an essential role in host defense
against infection. Macrophages not only bind and phagocytize P.
carinii, but are further activated to release a number of important
inflammatory products including reactive oxidants, arachidonic acid (AA)
metabolites and tumor necrosis factor alpha (TNFa). The mechanisms by
which macrophages bind and phagocytize P. carinii and become activated
to release inflammatory mediators are not well understood. Recent
studies suggest that the interaction of macrophages with P. carinii is
largely mediated by macrophage mannose receptors. The precise ligand
on P. carinii which is recognized by mannose receptors has not been
determined. P. carinii, however, contains a mannose-rich surface
glycoprotein termed gp120 which is the probable ligand for this
receptor. The application hypothesizes that gp120, a principal
component of P. carinii, interacts with macrophage mannose receptors and
the interaction of gp120 with macrophages mediates P. carinii binding
and phagocytosis and activates macrophage inflammatory systems including
AA metabolism, oxidant generation, and TNFa release. The Specific Aims
are to: 1) evaluate the interaction of purified gp120 with alveolar
macrophages; 2) purify and characterize gp120 receptors present on the
surface of alveolar macrophages; 3) evaluated the role of gp120 in
mediating the adherence of P. carinii to alveolar macrophages and in
initiation of phagocytosis; 4) investigate the role of gp120 in
activating macrophage inflammatory systems; and 5) determine the
expression of gp120 on isolated P. carinii cysts and trophozoites.
StatusFinished
Effective start/end date7/1/936/30/98

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)