A Role for Low Density Lipoprotein Receptor-Related Protein 1 in the Cellular Uptake of Tissue Plasminogen Activator in the Lungs.

ABSTRACT:

Purpose

To gain knowledge of lung clearance mechanisms of inhaled tissue plasminogen activator (tPA).

Methods

Using an in vivo mouse model and ex vivo murine whole organ cell suspensions, we examined the capability of the lungs to utilize LRP1 receptor-mediated endocytosis (RME) for the uptake of exogenous tPA with and without an LRP1 inhibitor, receptor associated protein (RAP), and quantitatively compared it to the liver. We also used a novel imaging technique to assess the amount LRP1 in sections of mouse liver and lung.

Results

Following intratracheal administration, tPA concentrations in the bronchoalveolar lavage fluid (BALF) declined over time following two-compartment pharmacokinetics suggestive of a RME clearance mechanism. Ex vivo studies showed that lung an

SUBMITTER: Lin S 

PROVIDER: S-EPMC4690798 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature