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. 2019 Jan 24;7(3):570–572. doi: 10.1002/ccr3.1989

M2‐polarized macrophages relate the clearance of gastric lanthanum deposition

Takahito Nakamura 1,, Atsunori Tsuchiya 2, Masayoshi Kobayashi 3, Makoto Naito 4, Shuji Terai 2
PMCID: PMC6406169  PMID: 30899497

Key Clinical Message

Previous reports have suggested that mucosal barrier failure allows lanthanum to stray into the lamina propria, and macrophages play an important role for the clearance. However, there is no report to analyze the polarity of phagocytizing macrophages. We suggested that M2 macrophage potentially played a major role in the clearance of lanthanum.

Keywords: dialysis, lanthanum, M2 macrophage, phagocytosis


Lanthanum carbonate (LC) is an oral phosphate binder to prevent hyperphosphatemia for patients undergoing dialysis. Recently, lanthanum‐deposited cases in the stomach have been reported (Table 1).1 On endoscopy, such deposits are recognized as minute whitish granules within mucosa (Figure 1A). Lanthanum deposition in patients taking LC is diagnosed based on detection of macrophages containing foreign body in the lamina propria (Figure 1B). Quantitative analysis of elemental composition by electron probe microanalysis confirms both lanthanum and phosphorus (Figure 1C). Macrophages generally can be divided into pro‐inflammatory type M1 and anti‐inflammatory type M2.2 However, the macrophage polarization involved in lanthanum clearance in the gastrointestinal tract has not been elucidated. We found that biopsy specimens from the stomach of 62‐year‐old man with diabetes mellitus, 2‐year history of dialysis, 9‐month history of LC administration, and no specific abnormal physical examination revealed massive eosinophilic infiltration positive for CD68 and CD206 (Figure 1D). CD68 is a common and general marker for both M1 and M2 macrophages, while CD206 is a marker to indicate M2 polarization. Therefore, we assume that phagocytizing M2 macrophages play an important role and M2 polarity induction can accelerate the clearance of lanthanum.2

Table 1.

Previously reported cases of lanthanum carbonate deposition

Authors Year Number of patients Age Co‐existing symptoms Duration of LC administration (mo) Dose of LC (mg/d) Deposition site Immunohistochemistry
Yasunaga 2015 1 64 Epigastric discomfort 50 1500 Stomach CD68, S100, Cam 5.2
Makino 2015 1 63 Heartburn and hiccups 41 500‐750 Stomach CD68
Haratake 2015 6 61‐69 Abdominal discomfort and pain 21‐49 500‐1500 Stomach and duodenum CD68, S100, Cam 5.2, Ki‐67
Rothenberg 2015 1 64 Low‐grade fever, nausea, diarrhea, and anorexia NA NA Stomach and duodenum CD68, CAM5.2, CD1a, S100
Tonooka 2015 1 81 Abdominal discomfort 7 750 Stomach NA
Goto 2016 19 NA NA NA NA Stomach and colon NA
Yabuki 2016 3 68‐77 None 3‐36 750‐1500 Stomach and duodenum CD68
Shitomi 2017 23 34‐82 Nausea, melena, abdominal pain, and discomfort 3‐67 500‐750 Stomach CD68
Hoda 2017 5 29‐66 Dysphagia, reflux, nausea, epigastric burn, melena, and early satiety 12‐72 3000‐6000 Stomach and duodenum NA
Murakami 2017 7 50‐79 Difficulty swallowing and appetite loss 5‐45 NA Stomach CD68
Iwamuro 2017 2 42, 73 None 25, 69 NA Stomach and duodenum CD68
Hattori 2017 16 47‐79 None 4‐65 500‐1500 Stomach and duodenum CD68
Nishikawa 2018 1 64 Nausea 72 750‐1500 Stomach NA
Iwamuro 2018 10 42‐76 NA 12‐86 NA Stomach and duodenum NA
Eso 2018 1 26 Epigastric discomfort and appetite loss 84 750 Stomach and duodenum CD68, PU.1

Figure 1.

Figure 1

Lanthanum deposition and their analysis (A‐D). Lanthanum deposits are recognized as minute whitish granules within mucosa by endoscopy (A). They are also recognized as eosinophilic infiltration in the lamina propria with hematoxylin and eosin staining (B). Quantitative analysis of elemental composition by electron probe microanalysis reveals macrophages include both lanthanum and phosphorus (yellow area; C). Macrophages are positive for CD206, indicating M2 polarization (D)

CONFLICT OF INTEREST

None declared.

AUTHOR CONTRIBUTION

All the authors: made substantial contribution to the preparation of this manuscript and approved the final version for submission. TN and AT: drafted the manuscript. AT: corresponding author. MK and MN: provided clinical support. ST: reviewed the manuscript.

Nakamura T, Tsuchiya A, Kobayashi M, Naito M, Terai S. M2‐polarized macrophages relate the clearance of gastric lanthanum deposition. Clin Case Rep. 2019;7:570–572. 10.1002/ccr3.1989

REFERENCES

  • 1. Murakami N, Yoshioka M, Iwamuro M, et al. Clinical characteristics of seven patients with lanthanum phosphate deposition in the stomach. Int Med. 2017;56(16):2089‐2095. [DOI] [PMC free article] [PubMed] [Google Scholar]
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