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Pathological and clinical relevance of selective recruitment of Langerhans cells in the respiratory bronchioles of smokers

Authors:	Aiko Masunaga Tamiko Takemura Hidenori Ichiyasu Emi Migiyama Yuko Horio Sho Saeki Susumu Hirosako Takeshi Mori Makoto Suzuki Hirotsugu Kohrogi Takuro Sakagami

Institution:	1. Department of Respiratory Medicine, Kumamoto University Hospital, Faculty of Life Sciences, Kumamoto University, Kumamoto, 860-8556, Japan;2. Department of Pathology, Kanagawa Cardiovascular and Respiratory Center, Kanagawa, 236-0051, Japan;3. Department of Thoracic Surgery, Kumamoto University Hospital, Faculty of Life Sciences, Kumamoto University, Kumamoto, 860-8556, Japan;1. Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-kogushi, Ube, 755-8505, Japan;2. Department of Medicine and Clinical Science, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-kogushi, Ube, 755-8505, Japan;1. Department of Pharmaceutics, Faculty of Pharmaceutical Science, Kobe Gakuin University, 1?1?3 Minatojima Chuo?ku Kobe City 650?8586, Japan;2. Department of Pharmacy, Kobe City Medical Center General Hospital, 2?1?1 Minatojima Minamimachi Chuo?ku Kobe City 650?0047, Japan;3. Department of Regulatory Science, Faculty of Pharmacy, Musashino University, 1?1?20 Shinmachi Nishitokyo City 202?8585, Japan;4. Department of Medical Oncology, Kobe City Medical Center General Hospital, 2?1?1 Minatojima Minamimachi Chuo?ku Kobe City 650?0047, Japan;5. Department of Medical Oncology, Takarazuka City Hospital, 4?5?1 Kohama Takarazuka City 655?0827, Japan;1. Department of Respiratory Medicine, Toho University School of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, 143-8541, Japan;2. Department of Physiology, School of Medicine, Faculty of Medicine, Toho University, 5-21-16 Omori-Nishi, Ota-ku, Tokyo, 143-8540, Japan;3. Division of Chest Surgery, Toho University School of Medicine, Omori-Nishi, Ota-ku, Tokyo, 6-11-1, Japan;4. Department of Advanced and Integrated Interstitial Lung Diseases Research, School of Medicine, Toho University, 5-21-16 Omori-Nishi, Ota-ku, Tokyo, 143-8540, Japan;1. Department of Medicine, School of Medicine, Chiba University, Chiba 260-8670, Japan;2. Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan;3. Health Professional Development Center, Chiba University Hospital, Chiba 260-8670, Japan;4. Department of Pulmonary Medicine, School of Medicine, International University of Health and Welfare, Chiba 286-8686, Japan;5. Department of General Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan;6. Department of Pathology, Chiba University Hospital, Chiba 260-8670, Japan;7. Department of Hematology, Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital, Tokyo 113-8677, Japan;8. Department of Hematology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan;9. Department of Hematology, School of Medicine, International University of Health and Welfare, Chiba 286-8686, Japan;1. Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan;2. Department of Radiology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan;3. Department of Infectious Diseases, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan;4. Department of Infection Control and Prevention, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan;5. Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan;6. Department of Orthopaedic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan;1. Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan;2. Department of Respiratory Medicine, Saitama Red Cross Hospital, Saitama, Japan;3. Department of Biostatistics, Yokohama City University School of Medicine, Yokohama, Japan

Abstract:	BackgroundSmoking causes an influx of inflammatory cells including Langerhans cells (LCs) into the airways and lung parenchyma, thus inducing histological changes, such as emphysema and fibrosis. We examined the distribution and quantity of Langerhans cells in relation to clinical and pathological findings and explored the association between smoking and accumulation of Langerhans cells in the respiratory bronchioles.MethodsFifty-three patients who underwent lung resection for primary diseases, including lung cancer, were recruited. Histological and immunohistochemistry analyses were utilized to identify CD1a-positive Langerhans cells in peripheral lung specimens separated from primary lesions. Clinical characteristics, pathological changes, and distribution of CD1a-positive Langerhans cells distribution were assessed.ResultsOf the 53 patients, 35 were smokers and 18 were non-smokers. The number of Langerhans cells in the respiratory bronchioles was significantly increased in smokers as compared to that in non-smokers (p < 0.001). The number of Langerhans cells in smokers was significantly higher in patients with mild emphysema than in those without emphysema (p < 0.01). The high-LC group showed more frequent smoking-related histological changes, such as respiratory bronchiolitis, parenchymal fibrosis, accumulation of macrophages, and smoking-related interstitial fibrosis, than the low-LC group. However, there were no differences in the smoking indices and pulmonary functions of the groups.ConclusionsSelective accumulation of Langerhans cells in the respiratory bronchioles of smokers may lead to the development of smoking-related pathological changes.

Keywords:	Cigarette smoking Emphysema Langerhans cell Respiratory bronchiole BALF"} {"#name":"keyword" "$":{"id":"kwrd0035"} "$$":[{"#name":"text" "_":"Bronchoalveolar lavage fluid BMI"} {"#name":"keyword" "$":{"id":"kwrd0045"} "$$":[{"#name":"text" "_":"Body mass index COPD"} {"#name":"keyword" "$":{"id":"kwrd0055"} "$$":[{"#name":"text" "_":"Chronic obstructive pulmonary disease CT"} {"#name":"keyword" "$":{"id":"kwrd0065"} "$$":[{"#name":"text" "_":"Computed tomography DC"} {"#name":"keyword" "$":{"id":"kwrd0075"} "$$":[{"#name":"text" "_":"Dendritic cell FEV1"} {"#name":"keyword" "$":{"id":"kwrd0085"} "$$":[{"#name":"text" "_":"Forced expiratory volume in one second FVC"} {"#name":"keyword" "$":{"id":"kwrd0095"} "$$":[{"#name":"text" "_":"Forced vital capacity H&E"} {"#name":"keyword" "$":{"id":"kwrd0105"} "$$":[{"#name":"text" "_":"Hematoxylin and eosin IQR"} {"#name":"keyword" "$":{"id":"kwrd0115"} "$$":[{"#name":"text" "_":"Interquartile range LC"} {"#name":"keyword" "$":{"id":"kwrd0125"} "$$":[{"#name":"text" "_":"Langerhans cell PFT"} {"#name":"keyword" "$":{"id":"kwrd0135"} "$$":[{"#name":"text" "_":"Pulmonary function test RB"} {"#name":"keyword" "$":{"id":"kwrd0145"} "$$":[{"#name":"text" "_":"Respiratory bronchiolitis SRIF"} {"#name":"keyword" "$":{"id":"kwrd0155"} "$$":[{"#name":"text" "_":"Smoking-related interstitial fibrosis UIP"} {"#name":"keyword" "$":{"id":"kwrd0165"} "$$":[{"#name":"text" "_":"Usual interstitial pneumonia VC"} {"#name":"keyword" "$":{"id":"kwrd0175"} "$$":[{"#name":"text" "_":"Vital capacity
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