title: Acute changes in sputum collected from exposed human subjects in mining conditions.
abstract: Neprilysin (NEP) is a key cell surface peptidase in the maintenance of airway homeostasis and the development of pulmonary disorders. However, little information is available about the effect of particulate matter (PM) on airway NEP. In this controlled human exposure study, changes in induced sputum were measured in 11 subjects at baseline, overshot (OS) mucking, and diesel exhaust (DE) exposure days. Neither OS condition nor DE exposure was found to induce significant changes in total protein, but DE induced significant increases in cell numbers of macrophages and epithelium. Moreover, significant increases in soluble NEP were observed following OS mining dust particulates (0.43 +/- 0.06 nmol/microg protein/min; p = .023) and DE exposure (0.40 +/- 0.03 nmol/microg protein/min; p = .035) when compared with the baseline control (0.30 +/- 0.04 nmol/microg protein/min), with 42% and 31% average net increase, respectively. Pearson's correlation analyses indicated that sputum NEP activity was significantly associated with personal exposure product (elemental carbon concentration [mg/m(3)] x time [min]; C x T). The data suggest that changes in NEP activity may be an early, accurate endpoint for airway epithelial injury and provide a new insight into the mechanism of airway effects following particulate exposure.
authors.affiliation: Department of Pediatrics, College of Medicine, 1501 N. Campbell Avenue, Tucson, AZ 85724-5073, USA. shengjun@email.arizona.edu
authors.forename: Simon S
authors.initials: SS
authors.lastname: Wong
authors.forename: Nina N
authors.initials: NN
authors.lastname: Sun
authors.forename: Hugh B
authors.initials: HB
authors.lastname: Miller
authors.forename: Mark L
authors.initials: ML
authors.lastname: Witten
authors.forename: Jefferey L
authors.initials: JL
authors.lastname: Burgess
mesh_terms: D000328:Adult; D000395:Air Pollutants, Occupational / Q000633:toxicity*; D015415:Biomarkers / Q000032:analysis; D002452:Cell Count; D005260:Female; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects / Q000032:analysis*; D008297:Male; D008906:Mining; D015260:Neprilysin / Q000032:analysis / Q000378:metabolism*; D052638:Particulate Matter / Q000633:toxicity*; D013183:Sputum / Q000166:cytology / Q000201:enzymology*; D018675:Toxicity Tests; D055815:Young Adult
chemical_list: D000395:Air Pollutants, Occupational; D015415:Biomarkers; D052638:Particulate Matter; D015260:Neprilysin
references.citation: Res Rep Health Eff Inst. 2000 Jun;94(Pt 2):5-70; discussion 71-9
references.pmid: 11354823
references.citation: N Engl J Med. 2007 Dec 6;357(23):2348-58
references.pmid: 18057337
references.citation: Clin Exp Allergy. 1999 Jun;29(6):813-23
references.pmid: 10336599
references.citation: Environ Health Perspect. 2002 Oct;110(10):1025-9
references.pmid: 12361928
references.citation: Am J Respir Crit Care Med. 2000 Jul;162(1):161-6
references.pmid: 10903236
references.citation: Arch Toxicol. 2003 Nov;77(11):638-50
references.pmid: 13680092
references.citation: J Pharmacol Exp Ther. 1989 Jan;248(1):7-11
references.pmid: 2464061
references.citation: Oncology. 2001;60(3):258-67
references.pmid: 11340378
references.citation: Nat Med. 1997 Aug;3(8):904-7
references.pmid: 9256283
references.citation: Science. 2005 May 6;308(5723):804-6
references.pmid: 15879201
references.citation: Eur Respir J. 1998 Dec;12(6):1454-62
references.pmid: 9877509
references.citation: Thyroid. 2003 Mar;13(3):291-5
references.pmid: 12729479
references.citation: Eur Respir J. 1995 Sep;8(9):1458-64
references.pmid: 8575569
references.citation: Am Rev Respir Dis. 1985 Dec;132(6):1262-7
references.pmid: 3000235
references.citation: Am J Physiol Lung Cell Mol Physiol. 2004 Oct;287(4):L859-66
references.pmid: 15194566
references.citation: J Clin Invest. 1994 Oct;94(4):1417-25
references.pmid: 7523450
references.citation: Res Rep Health Eff Inst. 2005 Jan;(128):1-37; discussion 39-47
references.pmid: 15916011
references.citation: Cancer Res. 1996 Feb 15;56(4):831-9
references.pmid: 8631021
references.citation: Am J Physiol. 1991 Apr;260(4 Pt 1):L212-25
references.pmid: 2018145
references.citation: Am J Respir Crit Care Med. 1999 Mar;159(3):702-9
references.pmid: 10051240
references.citation: Science. 1988 Sep 2;241(4870):1218-21
references.pmid: 2457950
references.citation: Nat Med. 1998 Jan;4(1):50-7
references.pmid: 9427606
references.citation: Ann N Y Acad Sci. 1996 Mar 22;780:156-63
references.pmid: 8602728
references.citation: Clin Toxicol (Phila). 2007;45(3):255-60
references.pmid: 17453876
references.citation: Epidemiology. 1997 May;8(3):298-303
references.pmid: 9115026
references.citation: JAMA. 2002 Mar 6;287(9):1132-41
references.pmid: 11879110
references.citation: Allergy. 2000 Apr;55(4):321-37
references.pmid: 10782516
references.citation: Proc Natl Acad Sci U S A. 1989 Sep;86(18):7103-7
references.pmid: 2528730
references.citation: Eur J Clin Invest. 1996 Nov;26(11):1011-7
references.pmid: 8957208
references.citation: Annu Rev Public Health. 1994;15:107-32
references.pmid: 8054077
references.citation: J Clin Invest. 1994 Jun;93(6):2667-74
references.pmid: 7515394
references.citation: J Clin Invest. 1989 Sep;84(3):900-6
references.pmid: 2474576
references.citation: Environ Health Perspect. 2002 Feb;110 Suppl 1:103-12
references.pmid: 11834468
references.citation: Am J Respir Crit Care Med. 1999 Mar;159(3):907-10
references.pmid: 10051271
references.citation: Occup Environ Med. 1996 Oct;53(10):658-62
references.pmid: 8943829
references.citation: Res Rep Health Eff Inst. 2003 Dec;(118):1-36; discussion 37-47
references.pmid: 14738210
references.citation: Ann N Y Acad Sci. 1986;465:738-43
references.pmid: 3014965
references.citation: Clin Cancer Res. 2000 May;6(5):1664-70
references.pmid: 10815884
references.citation: Am J Respir Cell Mol Biol. 1990 Sep;3(3):191-8
references.pmid: 1975191
references.citation: Science. 1996 Sep 20;273(5282):1722-5
references.pmid: 8781237
references.citation: J Appl Physiol (1985). 1999 Nov;87(5):1621-8
references.pmid: 10562600