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Urban particle-induced apoptosis and phenotype shifts in human alveolar macrophages.

Abstract：

:Epidemiological studies report a small but positive association between short-term increases in airborne particulate matter and small increases in morbidity and mortality from respiratory and cardiovascular disease in urban areas. However, the lack of a mechanistic explanation to link particle exposure and human health effects makes it difficult to validate the human health effects. The present study tested the hypothesis that urban particles could cause apoptosis of human alveolar macrophages(AM) and a shift of their phenotypes to a higher immune active state, which would provide a mechanism to explain an inflammatory response. Freshly isolated human AM were incubated for 24 hr with urban particles (#1648 and #1649), Mount Saint Helen's ash (MSH), and residual oil fly ash (ROFA). Cell viability was assessed by trypan blue exclusion and apoptosis was demonstrated by morphology, cell death ELISA, and DNA ladder formation. Additionally, AM were characterized according to RFD1(+) (immune stimulatory macrophages) and RFD1(+)7(+) (suppressor macrophages) phenotypes by flow cytometry. ROFA particles caused AM necrosis at concentrations as low as 10 microg/ml, urban particles had no effect except at 200 microg/ml, and MSH had no effect at 200 microg/ml. ROFA (25 microg/ml) and particles #1648 or #1649 (100 microg/ml) caused apoptosis of AM by all three criteria, but 200 microg/ml MSH had no effect. Finally, 25 microg/ml ROFA and 100 microg/ml particles #1648 or #1649 up regulated the expression of the RFD1(+) AM phenotype, while only ROFA decreased the RFD1(+)7(+) phenotype. Consequently, ROFA and urban particles can induce apoptosis of human AM and increase the ratio of AM phenotypes toward a higher immune active state (i.e., increased RFD1(+):RFD1(+)7(+) ratio). Ifurban particles cause similar changes in vivo, this could result in lung inflammation and possible increased pulmonary and cardiovascular disease.

journal_name

Environ Health Perspect

journal_title

Environmental health perspectives

authors

Holian A,Hamilton RF Jr,Morandi MT,Brown SD,Li L

doi

10.1289/ehp.98106127

subject

Has Abstract

pub_date

1998-03-01 00:00:00

pages

127-32

issue

eissn

0091-6765

issn

1552-9924

journal_volume

106

pub_type

杂志文章

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Urban particle-induced apoptosis and phenotype shifts in human alveolar macrophages.