title: Leukocytes are recruited through the bronchial circulation to the lung in a spontaneously hypertensive rat model of COPD.
abstract: Chronic obstructive pulmonary disease (COPD) kills approximately 2.8 million people each year, and more than 80% of COPD cases can be attributed to smoking. Leukocytes recruited to the lung contribute to COPD pathology by releasing reactive oxygen metabolites and proteolytic enzymes. In this work, we investigated where leukocytes enter the lung in the early stages of COPD in order to better understand their effect as a contributor to the development of COPD. We simultaneously evaluated the parenchyma and airways for neutrophil accumulation, as well as increases in the adhesion molecules and chemokines that cause leukocyte recruitment in the early stages of tobacco smoke induced lung disease. We found neutrophil accumulation and increased expression of adhesion molecules and chemokines in the bronchial blood vessels that correlated with the accumulation of leukocytes recovered from the lung. The expression of adhesion molecules and chemokines in other vascular beds did not correlate with leukocytes recovered in bronchoalveolar lavage fluid (BALF). These data strongly suggest leukocytes are recruited in large measure through the bronchial circulation in response to tobacco smoke. Our findings have important implications for understanding the etiology of COPD and suggest that pharmaceuticals designed to reduce leukocyte recruitment through the bronchial circulation may be a potential therapy to treat COPD.
authors.affiliation: Center for Health and the Environment, University of California Davis, Davis, California, United States of America. bbdavis@ucdavis.edu
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Davis
authors.forename: Yi-Hsin
authors.initials: YH
authors.lastname: Shen
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Tancredi
authors.forename: Vanessa
authors.initials: V
authors.lastname: Flores
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Davis
authors.forename: Kent E
authors.initials: KE
authors.lastname: Pinkerton
mesh_terms: D000818:Animals; D001980:Bronchi / Q000098:blood supply / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid; D004195:Disease Models, Animal; D006973:Hypertension / Q000150:complications / Q000473:pathology*; D007962:Leukocytes / Q000473:pathology*; D008297:Male; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000473:pathology*; D051381:Rats; D011918:Rats, Inbred SHR; D012906:Smoke; D014026:Nicotiana
chemical_list: D012906:Smoke