Novel properties of statins: suppression of the systemic and bone marrow responses induced by exposure to ambient particulate matter (PM(10)) air pollution.
Exposure to ambient particulate matter (PM(10) elicits systemic inflammatory responses that include the stimulation of bone marrow and progression of atherosclerosis. The present study was designed to assess the effect of repeated exposure of PM(10) on the turnover and release of polymorphonuclear leukocytes (PMNs) from the bone marrow into the circulation and the effect of lovastatin on the PM(10)-induced bone marrow stimulation. Rabbits exposed to PM(10)three times a week for 3 wk, were given a bolus of 5'-bromo-2'-deoxyuridine to label dividing cells in the marrow to calculate the transit time of PMNs in the mitotic or postmitotic pool. PM(10) exposure accelerated the turnover of PMNs by shortening their transit time through the marrow (64.8 ± 1.9 h vs. 34.3 ± 7.4 h, P < 0.001, control vs. PM(10)). This was predominantly due to a rapid transit of PMNs through the postmitotic pool (47.9 ± 0.7 h vs. 21.3 ± 4.3 h, P < 0.001, control vs. PM(10)) but not through the mitotic pool. Lovastatin delayed the transit time of postmitotic PMNs (38.2 ± 0.5 h, P < 0.001 vs. PM(10)) and shifted the postmitotic PMN release peak from 30 h to 48 h. PM(10) exposure induced the prolonged retention of newly released PMNs in the lung, which was reduced by lovastatin (P < 0.01). PM(10) exposure increased plasma interleukin-6 levels with significant reduction by lovastatin (P < 0.01). We conclude that lovastatin downregulates the PM(10)-induced overactive bone marrow by attenuating PM(10)-induced systemic inflammatory responses.
UBC James Hogg Research Centre, St. Paul’s Hospital, University of British Columbia, Vancouver, UK.
Ryohei
R
Miyata
Ni
N
Bai
Renaud
R
Vincent
Don D
DD
Sin
Stephan F
SF
Van Eeden
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D001973:Bromodeoxyuridine; D005260:Female; D015850:Interleukin-6 / Q000097:blood; D008148:Lovastatin / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D052638:Particulate Matter / Q000009:adverse effects*; D011014:Pneumonia / Q000139:chemically induced*; D011817:Rabbits
D015850:Interleukin-6; D052638:Particulate Matter; D008148:Lovastatin; D001973:Bromodeoxyuridine