ABSTRACT: Pulmonary alveolar proteinosis (PAP) is a rare disease of unknown
aetiology characterized by accumulations of lipoproteinaceous material within the
alveoli. The alveolar macrophages become increasingly foamy, and are thought to
have a role in the pathogenesis of PAP. However, the mechanisms of macrophage
recruitment are unclear.
In the bronchoalveolar lavage fluid (BALF) of four patients with PAP and 20
normal control subjects, the following were examined: the monocyte chemotactic
activity due to the chemokine monocyte chemoattractant protein (MCP)-1 with the
use of a chemotactic chamber assay, the levels of MCP-1 by enzyme-linked immunosorbent
assay, and the MCP-1 expression on lavage cells by immunocytochemistry
and in situ hybridization.
The monocyte chemotactic activity in the BALF of the PAP patients was markedly
elevated, and the activity was completely absorbed by treatment with anti-MCP-1.
The MCP-1 levels in the BALF were surprisingly high in the PAP group (25,100472
pg.mL-1), whereas low levels of MCP-1 were detected in the normal control subjects
(mean: never smokers 4.8; smokers 10.4 pg.mL-1). MCP-1 protein and messenger
ribonucleic acid were expressed by macrophages from the PAP patients, and the
expression was reduced according to foaming of the cells; there were monocyte-like
macrophages with strong expression, small foamy cells with moderate expression,
large foamy cells with a faint expression of MCP-1, and ghost cells with no expression.
However, the increase of macrophage number in the PAP BALF was relatively small.
These data suggest that monocyte chemoattractant protein-1 expression by alveolar
macrophages represents an amplification mechanism for the recruitment of additional
macrophages to the alveoli in pulmonary alveolar proteinosis. It is possible that an
ingestion of an excess of alveolar materials in pulmonary alveolar proteinosis may
impair the macrophage function and the survival, resulting in the lack of a prominent
increase in the macrophage number in bronchoalveolar lavage fluid.