Enhanced expression of the mannose receptor by endothelial cells of the liver and spleen microvascular beds in the macrophage-deficient PU.1 null mouse.

Mice null for the haematopoietic lineage-specific transcription factor PU.1 lack mature Mphi and are compromised in their ability to clear cellular debris from the blood circulation. We investigated the possibility that non-professional phagocytes may partially compensate for the lack of Mphi in clearance functions. In the absence of Kupffer cells (resident liver Mphi) in the PU.1 null mice, electron microscopy revealed ingested debris in sinusoidal endothelial cells and hepatocytes although debris was also seen free in blood vessels. To investigate whether an increased clearance function of non-professional phagocytes might be linked to expression of Mphi-associated phagocytic and pinocytic receptors by other cells in PU.1 null mouse, we examined expression of several candidate proteins by immunocytochemistry and Western blotting. We found mannose receptor (MR) comparably expressed in PU.1 null and PU.1+ mice liver and spleen whereas class A scavenger receptor was substantially reduced and complement receptor 3 was absent in PU.1 null animals. By morphometric analysis, liver and spleen sinusoidal endothelial cells were seen to express significantly more MR in the PU.1 null mouse. This study provides the first evidence of apparently compensatory alterations in the microvasculature of the Mphi-deficient PU.1 null mouse.