백서의 폐포 및 복강 대식세포의 세포독성에 대한 연구

이홍렬(Hong Lyeol Lee),김세규(Se Kyu Kim),장준(Joon Chang),김성규(Sung Kyu Kim),이원영(Won Young Lee),조철호(Chul Ho Cho) 대한내과학회 1992 대한내과학회지 Vol.43 No.4

N/A Background: Mechanisms involved in host resistance against malignant tumors have been found to be mediated mainly by cellular effectors. These effector mechanisms include activated macrophages, killer T-cells, natural killer cells and antibody-dependent cellmediated cytotoxicity. Activated macrophages can sup- press DNA synthesis of tumor cells and kill tumor cells in a selective but nonspecific fashiori in vitro. Lipopolysaccharides (LPS) can enhance the cytotoxicity of macrophages and the lipid A which is produced by mild acid hydrolysis of LPS, is responsible for the LPS effect on macrophages. The mechanism by which LPS modifies macrophage physiology is not known, but it is suggested that it acts at the level of the macrophage plasma membrane. LPS may make macrophages tumoricidal by altering the membrane composition or by transmitting a necessary signal from the membrane to the vacuolar system. Methods: We isolated alveolar and peritoneal macrophages by bronchoalveolar and peritoneal lavage in rats. Rat sarcoma cell line (XC) was used as the target cell. As recommended commonly we controlled the effector cell: target cell ratio at 10:1, Three groups were divided as folows; no LPS added group, LPS 5μg/ml added group and LPS 10μg/ml added group, We focused the assay of cytotoxicity on the cytolysis rather than cytostasis by measuring the [3H] thymidine released and calculated the percentage specific cytalysis, By this experiment, we examined the stimulation effect of LPS an the macrophage cytotoxicity and compared the cytotoxicity between alveolar and peritoneal macrophages. Results: The cytotoxicity of alveolar and peritoneal macrophages was significantly enhanced when stimulated both with 5μg/ml and 10μg/ml of LPS. There was no significant difference in macrophage cytotoxicity between two groups each stimulated with 5μg/ml and 10μg/ml of LPS. We could not observe the significant difference in cytotoxicity between the alveolar and peritoneal macrophages, Conclusion: Cytotoxicity was significantly enhanced by stimulation of LPS, in hoth alveolar and peritoneal macrophages but there was no significant difference in cytotoxicity enhancement between 5μg/ml and 10μg/ ml of LPS. Also there was no significant difference in cytotoxicity between alveolar and peritoneal macrophages.

Interleukin-1의 기관지 투여 후 나타나는 폐세척액 내 대식세포의 수적변화에 따른 Xanthine Oxidase의 활성변화

조현국,윤종국,최정목,박원학,이영만,Cho, Hyun-Gug,Yoon, Chong-Guk,Choi, Jeung-Mok,Park, Won-Hark,Lee, Young-Man 한국현미경학회 2001 Applied microscopy Vol.31 No.3

The pulmonary alveolar macrophage is thought to play an important role in the mediation of acute inflammatory lung injury by secretory products including degraded enzymes, cytokines, and reactive oxygen metabolites . This study was conceived to understand the role of alveolar macrophage in oxidative stress induced acute lung injury. To examine the alveolar macrophages and xanthine oxidase (XO) activity in bronchoalveolar lavage fluid (BALF), time-dependent changes of numbers of alveolar macrophages, monocytes and neutrophils in alveolar cavity were counted in association with ultrastructural and cytochemical observations of lung tissue and alveolar cells. The number of monocytes was increased (p<0.001) at 1h after IL-1 treatment compared with that of sham. At 2h after instillation of IL-1, the number of alveolar macrophages was the highest, XO activity in BALF was elevated at 2h after IL-1 instillation and the activity was markedly elevated(p<0.05) at 3h after IL-1 treatment. On the basis of these experimental results, it is suggested that, during early phase of acute lung injury induced by IL-1, alveolar macrophage-derived XO contributes to lung injury earlier than the neutrophilic respiratory burst. 폐포강 대식세포는 사이토카인, 유해산소 대사물을 포함한 그들이 분비하는 물질들로 인해 급성 폐손상에 있어서 직접, 간접적으로 폐손상의 초기반응에 중요한 역할을 담당하는 것으로 알려져 있다. 본 연구에서는 $interleukin-1\alpha$(IL-1)로 유도된 급성 폐손상에서 폐포강 대식세포의 역할을 알아보고자 하였다. 실험군은 대조군과 IL-1투여 후 1시간, 2시간, 3시간, 4시간 그리고 5시간군으로 나누었으며, 폐포강 대식세포와 XO와의 관계를 분석하기 위해 폐세척액 내 XO의 활성도와 폐포강 대식세포, 단핵구, 그리고 호중구의 수적 변화를 측정하였다. 그리고 각 군의 미세구조 변화를 관찰하였다. 실험 결과, 폐포강 내 단핵구의 수는 IL-1투여 후 1시간군에서 대조군과 비교하여 현저히 증가되었으며 (p<0.001), 폐포강 대식세포의 수는 IL-1 투여 2시간 후에 가장 높았고, 폐세척액 내 XO의 활성도는 IL-1 투여 후 점차적으로 증가되다가 3시간 후에 현저히 증가되었다(p<0.05). 폐포강 내 호중구의 수는 IL-1투여 3시간 후부터 뚜렷이 증가되기 시작하였다. 이러한 결과로 보아 IL-1을 기관지 내로 투여한 후 유도된 급성 폐손상에서 폐포강 대식세포에서 유리된 XO는 호중구의 축적에 의한 손상보다 더 초기단계에서 폐손상을 유도하는 인자인 것으로 추정된다.

ACT001 alleviates inflammation and pyroptosis through the PPAR-γ/NF-κB signaling pathway in LPS-induced alveolar macrophages

Fu Qiang,Shen Na,Fang Tao,Zhang Hewei,Di Yanbo,Liu Xuan,Du Chao,Guo Jianshuang 한국유전학회 2024 Genes & Genomics Vol.46 No.3

Background ACT001 is an anti-inflammatory agent that has been widely investigated for its role in tumors, intracranial diseases, and fibrotic diseases, but its effect on acute lung injury is less known. Objective The purpose of this study was to investigate the effect and mechanism of ACT001 on regulating inflammation and pyroptosis in lipopolysaccharide (LPS)-induced alveolar macrophages. Methods NR8383 alveolar macrophages treated with LPS were used to replicate the proinflammatory macrophage phenotype observed during acute lung injury. After ACT001 treatment, we measured the secretion and expression levels of critical inflammatory cytokines, the rate of pyroptosis, and the expression of NLRP3 inflammasome-associated proteins and pyroptosis-associated proteins. In addition, we assessed the role of the PPAR-γ/NF-κB signaling pathways and further validated the results with a PPAR-γ inhibitor. Results Our findings confirmed that ACT001 reduced the expression and release of inflammatory factors, attenuated cell pyroptosis, and downregulated the expression of NLRP3, ASC, caspase-1 p20, and GSDMD-N. These effects may be achieved by activating PPAR-γ expression and then inhibiting the NF-κB signaling pathway. When macrophages were treated with the PPAR-γ inhibitor, the protective effects of ACT001 were reversed. Conclusion ACT001 significantly ameliorated inflammation and pyroptosis via the PPAR-γ/NF-κB signaling pathways in LPS-induced NR8383 alveolar macrophages. Background ACT001 is an anti-inflammatory agent that has been widely investigated for its role in tumors, intracranial diseases, and fibrotic diseases, but its effect on acute lung injury is less known. Objective The purpose of this study was to investigate the effect and mechanism of ACT001 on regulating inflammation and pyroptosis in lipopolysaccharide (LPS)-induced alveolar macrophages. Methods NR8383 alveolar macrophages treated with LPS were used to replicate the proinflammatory macrophage phenotype observed during acute lung injury. After ACT001 treatment, we measured the secretion and expression levels of critical inflammatory cytokines, the rate of pyroptosis, and the expression of NLRP3 inflammasome-associated proteins and pyroptosis-associated proteins. In addition, we assessed the role of the PPAR-γ/NF-κB signaling pathways and further validated the results with a PPAR-γ inhibitor. Results Our findings confirmed that ACT001 reduced the expression and release of inflammatory factors, attenuated cell pyroptosis, and downregulated the expression of NLRP3, ASC, caspase-1 p20, and GSDMD-N. These effects may be achieved by activating PPAR-γ expression and then inhibiting the NF-κB signaling pathway. When macrophages were treated with the PPAR-γ inhibitor, the protective effects of ACT001 were reversed. Conclusion ACT001 significantly ameliorated inflammation and pyroptosis via the PPAR-γ/NF-κB signaling pathways in LPS-induced NR8383 alveolar macrophages.

Platelet-Activating Factor Potentiates the Activity of Respiratory Burst and Interleukin-1 in Rat Alveolar Macrophages

Lee, Ji Hee 이화여자대학교 생명과학연구소 1995 생명과학연구논문집 Vol.6 No.-

The objective of the present study was to test the effect of platelet-activating factor (PAF) on rat alveolar macrophages. PAF alone did not simulate superoxide secretion from alveolar macrophages. However, PAF (10^-5M) significantly enhanced phagocytic activator zymosan-induced superoxide secretion from alveolar macrophages. This enhancement of PAF plus zymosan was 30% above the sum of the separate effects of PAF and zymosan. Similarly, PAF (1.3×10^-5M) was not a direct stimulant of alveolar macrophages, as it had no stimulatory effect on chemiluminescence generation, but potentiated zymosan-induced activation of chemiluminescence, i.e., 162% above the separate effects of each stimulant. PAF (10^-16~10^-6M) also failed to stimulate IL-1 production from alveolar macrophages. In contrast, when both PAF (10^-10M) and lipopolysaccharide(LPS) (1㎍/㎖) were added together at the initiation of the culture, IL-1 production by alveolar macrophages. Collectively, these data suggest that PAF alone does not activate the release of bioactive products from alveolar macrophages. However, PAF appears to act as a priming mediator that potentiates stimuli-induced macrophage activity. These novel actions of PAF prove its role as a potent mediator of inflammatory and immune responses in the lung.

Platelet-Activating Factor Potentiates the Activity of Respiratory Burst and Interleukin-1 in Rat Alveolar Macrophages

Lee. Ji-Hee 대한생리학회 1995 대한생리학회지 Vol.29 No.2

The objective of the present study was to test the effect of platelet-activating factor (PAF) on rat alveolar macrophages. PAF alone did not stimulate superoxide secretion from alveolar macrophages. However, PAF (10^-5 M) significantly enhanced phagocytic activator zymosan-induced superoxide secretion from alveolar macrophages. This enhancement of PAF plus zymosan was 30% above the sum of the separate effects of PAF and zymosan. Similarly, PAF 1.3 X (10^-5 M) was not a direct stimulant of alveolar macrophages, as it had no stimulatory effect on chemiluminescence generation, but potentiated zymosan-induced activation of chemiluminescence, i.e., 162% above the separate effects of each stimulant. PAF 10^-16±10^-6 M also failed to stimulate IL-1 production from alveolar macrophages. In contrast, when both PAF 10^-10 M and lipopolysaccharide(LPS) (1 μg/ml) were added together at the initiation of the culture, IL-1 production was significantly increased indicating the potentiative effects of PAF on IL-1 production by alveolar macrophages. Collectively, these data suggest that PAF alone does not activate the release of bioactive products from alveolar macrophages. However, PAF appears to act as a priming mediator that potentiates stimuli-induced macrophage activity. These novel actions of PAF prove its role as a potent mediator of inflammatory and immune responses in the lung.

Interleukin-1β에 의하여 치주인대세포에서 유리된 cytokine이 파골세포형성에 미치는 영향

이종갑,곽월아,유윤정,이승일,김태선 大韓小兒齒科學會 1996 大韓小兒齒科學會誌 Vol.23 No.1

Tooth movement is induced by bone remodeling during orthodontic treatment. Bone remodeling is regulated by various cytokines. Especially interleukin-1 (IL-1β), a cytokine present in periodontal ligaments of experimentally moved teeth, elicits bone resorption. In these processes, IL-1-induced bone resorption is mediated by interleukin-6 (IL-6) and granulocyte macrophage-colony stimulating fector (GM-CSF) secreted from osteoblasts. Periodontal ligament cells, which function as an anchorage for tooth, lie between alveolar bone and cementum. Therefore cytokines produced in the periodontal ligament (PDL) cells may also directly affect alveolar bone resorption in orthodontic tooth movement. Here I have examined whether PDL cells express IL-1β,interleukin-6 (IL-6) and granulocyte macrophage-colony stimulating factor (GM-CSF) mRNA and secrete those cytokines in response to IL-1β. Finally I have investigated whether IL-6 produced from PDL cells induces osteoclast formation in mouse bone marrow cell cultures. The expression of mRNA was estimated by polymerase chain reaction (PCR). The concentration of cytokines was quantified using enzyme linked immunosorbent method and the osteoclasts in bone marrow cultures were identified by tartrate resistant acid phosphatase (TRAP) stain. As results of these studies, IL-1βstimulated the expression of IL-1β, IL-6 and GM-CSF mRNA in PDL cells. 0.05 ng/ml IL-1βalso induced maximum production of Il-6 and GM-CSF in these cells. After an addition of IL-1β(0.05 ng/ml), IL-6 production increased from 2 hours to 8 hours and GM-CSF production also increased from 4 hours to 8 hours. IL-6 (100 ng/ml) increased the number of TRAP positive multinucleated cells in the presence of soluble interleukin-6 receptor (sIL-6R, 100 ng/ml). These results suggest that IL-1βmay stimulate alveolar bone resorption by inducing IL-6 and GM-CSF production in PDL cells which enhance osteoclast differentiation and IL-6 enhances osteoclast formation in the presence of sIL-6R. And this process by IL-1βmay be closely associated with alveolar bone resorption induced by orthodontic force.

소청용장(小靑龍湯)이 생쥐의 폐(肺) 대식세포(大食細胞) Cytokine 귀전자(遣傳子) 발현에 미치는 영향

박인기,심성용,변학성,김경준,Park, In-Gi,Sim, Sung-Young,Byun, Hak-Sung,Kim, Kyung-Jun 대한한방안이비인후피부과학회 2005 한방안이비인후피부과학회지 Vol.18 No.3

In many recent studies, molecular biological methods have been used to investigate the role of cytokines in pathogenesis of lung disease. This Experiment was conducted to investigate the effects of Sochungyong-tang on gene expressions in Mouse Alveolar Macrophage. Fer this purpose, we observed the cytokines ($IL-1{\beta}$, IL-6, IL-10, iNOS, $MIP-1{\alpha},\;MIP-1{\beta},\;MIP-1{\gamma},\;TGF-{\beta},\;TNF-{\alpha}$). We picked the alveolar macrophage out of mice and cultured it. We analyzed the cytokine gene expression by reverse transcription-PCR. The results obtained were as follows : 1 . Sochungyong-tang showed inhibitory effects on $IL-1{\beta}$ in time and concentration. 2. Sochungyong-tang showed inhibitory effects on IL-6 in time and concentration. 3. Sochungyong-tang showed inhibitory effects on IL-10 in concentration. 4. Sochungyong-tang showed inhibitory effects on iNOS. 5. Sochungyong-tang showed inhibitory effects on $TGF-{\beta}$ in time and concentration. 6. Sochungyong-tang showed on inhibitory effects on $MIP-1{\alpha},\;MIP-1{\beta},\;MIP-1{\gamma}$, $TCF-{\beta}$, $TNF-{\alpha}$. According to above results, it is supposed that Sochungyong-tang has the inhibitory effects on cytokine gene expression in mouse alveolar macrophage and can be usefully applied for curing inflammatory process of lung disease. Advanced studies are required to investigate the cure mechanism of Sochungyong-tang in the future.

미세분진이 흰쥐의 폐포대식세포에서 TNF-α와 IL-1β의 형성에 미치는 효과

리천주 ( Tian Zhu Li ),이수진 ( Soo Jin Lee ),박세종 ( Se Jong Park ),장병준 ( Byung Joon Chang ),이종환 ( Jong Hwan Lee ),김길수 ( Kil Soo Kim ),이명헌 ( Myoung Heon Lee ),최농훈 ( Nong Hoon Choe ) 대한결핵 및 호흡기학회 2006 Tuberculosis and Respiratory Diseases Vol.60 No.5

연구배경: 대도시의 대기오염은 점차 악화되어 시민의 건강을 위협하고 심,폐 질환의 발병률과 이로 인한 사망률을 증가시키고 있다. 서울시 도로가의 PM이 TNF-α와 IL-1β의 생성에 직접적으로 어떠한 영향을 미치는지와 PM의 노출이 LPS의 TNF-α와 IL-1β의 생성효과에는 어떠한 영향을 미치는지를 평가하고자 하였다. 방법: 폐렴이 있는 흰쥐와 SPF 흰쥐의 폐포대식 세포 각각에 PM을 농도별로 처리하여 분비되는 TNF-α와 IL-1β의 농도를 측정하였다. 측정 방법으로는 western blot, ELISA 및 세포면역화학염색법을 이용하였다. 또한 동일 PM 농도에서 배양시간을 달리하여 위와 같이 측정하였다. 결과: SPF인 흰쥐에서 분리된 폐포대식세포에 PM을 단독으로 투여하였을 때 대조군에 비해서 TNF-α와 IL-1β의 생성도가 모든 투여군에서 유의하게 증가하였으나, 투여용량의 증가에 따른 유의성은 없었다. 그러나 염증성인 쥐에서 분리된 폐포대식세포에서는 모든 투여군에서 대조군에 비하여 통계 학적으로 유의하게 증가하였으며, PM 투여농도의 증가에 따른 생성량도 유의하게 증가하였다. 결론: PM을 장기간 혹은 일정 농도 이상으로 흡입할 경우 폐포대식세포의 TNF-α와 IL-1β의 분비에 영향을 미쳐 새로운 폐질환을 유발할 수 있다. 그러므로 기존에 염증성 폐질환이나 기관지천식이 있는 환자가 미세먼지를 흡입할 경우에는 TNF-α와 IL-1β의 생성에 커다란 영향을 미쳐 호흡기 질환을 더욱 악화시킬 가능성이 있을 것으로 추정된다. Background: PM is known to induce various pulmonary diseases, including asthma, cancer, fibrosis and chronic bronchitis. Despite the epidemiological evidence the pathogenesis of PM-related pulmonary diseases is unclear. Methods: This study examined the effects of PM exposure on the secretion of TNF-α and IL-1β in the cultured alveolar macrophages. The cultured primary alveolar macrophages were treated with the medium, PM (5~20㎍/㎠), LPS (5ng/ml), and PM with LPS for 24h and 48h respectively. ELISA was used to assay the secreted TNF-α and IL-β in the culture medium. Western blotting was used to identify and determine the level of proteins isolated from the culture cells. The cells cultured in the Lab-Tek(R) chamber slides were stained with immunocytochemical stains. Results: PM induced TNF-α and IL-1β secretion in the culturing alveolar macrophages, collected from the SPF and inflammatory rats. However, the effects were only dose-dependent in the inflammatory macrophages. When the cells were co-treated with PM and LPS, there was a significant synergistic effect compared with the LPS in the both cell types. Conclusion: PM might be play an important role in the induction and/or potentiation of various lung diseases by oversecretion of TNF-α and IL-1β. (Tuberc Respir Dis 2006; 60: 554-563)

Studies on the prevention of tuberculosis in pet dogs 1. The effects of BCG pretreatment in pet dogs inoculated experimentally with Mycobacterium bovis

강종구,김창기,Kang, Jong-koo,Kim, Chang-ki The Korean Society of Veterinary Science 1992 大韓獸醫學會誌 Vol.32 No.1

Mycobacterium (M) bovis 를 인공감염시킨 개에 있어서 BCG의 전처치효과를 in vivo 및 in vitro에서 검토하였다. 개들은 BCG 전처치군, M bovis 단독처치군, 비감염대조군의 세군으로 나누었다. BCG는 M bovis 복강접종 3주일전에 0.2ml를 피내접종하였다. 결핵균 투여 4개월후에 전군을 도살하여 실험에 사용하였다. 도살시 모든 처치군에서 감염이 확인되었다. 병리조직학적으로 BCG전처치군의 폐장내에서는 경도의 macrophage의 침윤과 소상의 육아종 형성이 관찰되였으나 M bovis 단독처치군에 있어서는 보다 고도의 macrophage의 침윤, 중등도의 호중구의 침윤 및 중등도의 육아종의 형성이 확인되었다. 각 동물의 기관지폐포세정액을 분리하여 그 속의 총세포수와 각 세포의 분획을 검토하였다. 비감염 대조군의 기관지폐포세정액내의 총세포수는 두 처치군보다 훨씬 낮았으며 M bovis 단독처치군의 총세포수는 BCG 전처치군보다 1.8배 높았다. 이 세정액으로부터 폐포 macrophage를 분리배양하여 macrophage의 활성능과 결핵균의 증식능을 관찰하였다. BCG처치군은 M bovis 단독처치군에 비하여 높은 Fc receptor 활성(rosette 형성능, 탐식능)과 낮은 결핵균의 증식이 관찰되었다. 그러나 BCG의 전처치는 결핵균을 killing하지는 못하였다. 개에게 BCG를 전처치하면 폐내에 극소수의 결핵균이 지속적으로 잔존하지만 폐포 macrophage는 이미 항결핵성면역능을 지닌채로 계속 활성화된 상태로 존재하기 때문에 결핵에 대하여 예방효과를 갖는다고 사료된다. Dogs were divided into 3 groups of two each; Bacillie Calmette-Guerin(BCG) pretreatment, M bovis only treatment and uninfected control group. BCG were vaccinated intradermally with 0.2ml before 3weeks of M bovis intraperitoneal infection. Infection at necropsy 4months later was readily in the both treated dogs. Histopathologically, the BCG pretreated dogs produce the moderate accumulation of macrophages and focal granuloma formation in the lung, whereas the M bovis only treared dogs produce the accumulation of predominantly macrophages, occasionaly polymorphonuclear cells and the more larger granuloma Bronchoalveolar lavage(BAL) was obtained and total and differential cell counts were examined. Total number of BAL cells harvested from uninfected dogs is lower compared with those of the both treated groups. The total cell number of M bovis only treated dogs were singificantly higher 1.8 times than that of the BCG pretreated dogs. The Fe receptor activity and the growth of organism in alveolar macrophages obtained from BCG pretreated dogs were compared with that in macrophages from M bovis only treated dogs. BCG vaccination resulted in substantial macrophage activation, measured as increased Fc receptor mediated phagocytosis and rosette formation, as wells as the inhibition of intracellular mycobacteria multiplication. However, actibated macrophages taken from BCG pretreated dogs are incapable of killing the M bovis. Thus, these results suggest that BCG pretrearment in the dog may produce a protective effect against tuberculosis because active alveolar macrophages have acquired antituberculous immunity, although few mycobacteria within the lung remain in a metabolically active state.

ATP6V0d2 Suppresses Alveoli Macrophage Alternative Polarization and Allergic Asthma via Degradation of PU.1

Liu Na,Feng Yuchen,Liu Huicheng,Wu Wenliang,Liang Yuxia,Li Pingfei,Wei Zhengping,Wu Min,Tang Zhao-Hui,Han Junyan,Cheng Xiang,Liu Zheng,Laurence Arian,Li Huabin,Zhen Guohua,Yang Xiang-Ping 대한천식알레르기학회 2021 Allergy, Asthma & Immunology Research Vol.13 No.3

Purpose Macrophages are important regulators of environmental allergen-induced airway inflammation and asthma. ATP6V0d2 is a subunit of vacuolar ATPase highly expressed in macrophages. However, the functions of ATP6V0d2 in the regulation of pathogenesis of allergic asthma remain unclear. The aim of this study is to determine the function and related molecular mechanisms of macrophage protein ATP6V0d2 in allergic asthma. Methods We compared the disease severity between female C57BL/6 wild-type and ATP6V0d2−/− mice in an ovalbumin (OVA)-induced asthma model. We also investigated the association of expression of ATP6V0d2, PU.1 and CCL17 with disease severity among asthmatic patients. Results The expression of ATP6V0d2 in sputum cells of asthmatic patients and in the lungs of OVA-challenged mice was enhanced compared to healthy subjects and their counterparts, respectively. However, ATP6V0d2-deficient mice exaggerated inflammatory cell infiltration as well as enhanced alternative activated macrophage (AAM) polarization and mucus production in an OVA-induced asthma model. Furthermore, we found that Atp6v0d2 promoted lysosomal degradation of Pu.1, which induced AAM polarization and Ccl17 production. Among asthma patients, ATP6V0d2 expression was inversely associated with disease severity, whereas PU.1 and CCL17 expression was positively associated with disease severity. Conclusions Our results identify macrophage Atp6v0d2, as an induced feedback inhibitor of asthma disease severity by promoting Pu.1 lysosomal degradation, which may in turn leads to reduced AAM polarization and Ccl17 production.