[The effect of foamy alveolar macrophages presented in bleomycin-injured rat lungs in pulmonary fibrosis].
Foamy alveolar macrophages (FAM) are observed in lungs injured by Bleomycin (BLM), but their relation to pulmonary fibrosis is not clearly understood. We purified FAM from BLM-instilled rat lungs by density gradient centrifugation on Percoll, and studied the effect of FAM on pulmonary fibrosis. The cells lavaged from the rat lungs 14 days after the administration of BLM (B) or saline (S), were applied on Percoll. After centrifugation, the cells layered on each interface were collected and named as SI, SII, SIII, and BI, BII, BIII in order of gravity. The BI layer included 8.5% of unfractionated cells (U). These BI cells were viable (88%), significantly larger than the others, nonspecific esterase positive cells, and included much ferritin and lysozyme, and were morphologically identified as alveolar macrophages (AM). Therefore, we called the BI cells FAM. We estimated the capacity of FAM (2.5 X 10(5] to synthesize DNA (3H-thymidine uptake) and RNA (3H-uridine uptake), and the activities of silica-stimulated FAM to cause proliferation of mouse thymocytes (IL-1 activity) and rat lung fibroblasts (FP activity), and to produce PGE2. FAM has a lower mitogenic activity but did not have been protein synthetic activity as compared with the others. Silica-stimulated FAM released less IL-1 than BII or BIII, and induced less fibroblast growth than BII, but induced as much as BIII, possibly because of the increased capacity of BIII cells to produce PGE2, which is known to inhibit fibroblast growth. In this way, FAM were considered to be "already activated" rather than "highly activated" cells, but the presence of FAM suggested that smaller or denser AM might receive bleomycin stimulation and release fibrogenic mediators (IL-1 or MDGF) into the alveolar spaces during FAM formation, and that AM might participate in the fibrogenic responses.
Suwabe
A
A
Nakamura
H
H
Yakuwa
N
N
Igarashi
K
K
Higuchi
J
J
Takahashi
K
K
Yasui
S
S
D000818:Animals; D001761:Bleomycin / Q000009:adverse effects*; D007375:Interleukin-1 / Q000378:metabolism / Q000502:physiology; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D011650:Pulmonary Alveoli / Q000166:cytology; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology*; D051381:Rats; D011919:Rats, Inbred Strains
D007375:Interleukin-1; D001761:Bleomycin