Claudin-3 and Clara cell 10 kDa protein as early signals of cigarette smoke-induced epithelial injury along alveolar ducts.
Smoking-associated chronic obstructive pulmonary disease is characterized by inflammation, changes affecting small airways, and development of emphysema. Various short- and long-term models have been introduced to investigate these processes. The aim of the present study was to identify markers of early epithelial injury/adaptation in a short-term animal model of cigarette smoke exposure. Initially, male BALB/c mice were exposed to smoke from one to five cigarettes and lung changes were assessed 4 and 24 hr after smoking cessation. Subsequently, animals were exposed to smoke from five cigarettes for 2 consecutive days and lungs investigated daily until the seventh postexposure day. Lung homogenates cytokines were determined, bronchioloalveolar fluid cells were counted, and lung tissue was analyzed by immunohistochemistry. Exposure to smoke from a single cigarette induced slight pulmonary neutrophilia. Smoke from two cigarettes additionally induced de novo expression of tight junction protein, claudin-3, by alveolar duct (AD) epithelial cells. Further increases in smoke exposure induced epithelial changes in airway progenitor regions. During the recovery period, the severity/frequency of epithelial reactions slowly decreased, coinciding with the switch from acute to a chronic inflammatory reaction. Claudin-3 and Clara cell 10 kDa protein were identified as possible markers of early tobacco smoke-induced epithelial injury along ADs.
GlaxoSmithKline Research Centre Zagreb Limited, Zagreb, Croatia. snjezana.cuzic@glpg.com
Snjezana
S
Cuzić
Martina
M
Bosnar
Miroslava Dominis
MD
Kramarić
Zeljko
Z
Ferencić
Darko
D
Marković
Ines
I
Glojnarić
Vesna
V
Eraković Haber
D056809:Alveolar Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D062465:Claudin-3 / Q000378:metabolism*; D004195:Disease Models, Animal; D019570:Inhalation Exposure; D007958:Leukocyte Count; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D012907:Smoking / Q000009:adverse effects*; D013997:Time Factors; D014598:Uteroglobin / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein / Q000378:metabolism; D014026:Nicotiana
D015415:Biomarkers; D062465:Claudin-3; C556389:SCGB1A1 protein, human; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; D014598:Uteroglobin