Arsenic immunotoxicity: a review

Dangleben, Nygerma L; Skibola, Christine F; Smith, Martyn T

doi:10.1186/1476-069X-12-73

Environmental Health

Table 1 Major findings of As-associated immune-related effects that are consistent across multiple studies

From: Arsenic immunotoxicity: a review

Immune parameter	Major findings	Study model	Description	References
Defense genes/proteins	↓ MHC class II	Humans	PBMC mRNA	[19]
		Animals	Mouse macrophage surface expression	[106]
	↓ CD69	Humans	PBMC mRNA	[19]
		Human cells	PBMC surface expression	[122]
		Animal cells	Mouse SMC surface expression	[115]
	↓ IL-1β	Humans	PBMC mRNA	[19, 20]
		Animals	Mouse lung mRNA & protein	[82, 110]
			Zebrafish mRNA	[83]
	↑ CD14	Humans	PBMC mRNA & surface expression	[21, 30]
		Human cells	Macrophage surface expression	[130, 131]
	↓ TNF-α	Humans	PBMC mRNA	[20, 22]
			PBMC secretion	[26]
		Animals	Zebrafish mRNA	[84]
			Rat PAM secretion	[104]
			Mouse lung fluid protein	[110]
Inflammation	↑ Expression of inflammatory mediators	Humans	↑ PBMC IL1B, IL6, CCL2 & CD14 mRNA in adults	[21]
			↑ PBMC CD14 surface expression & TNF-α secretion in adults	[30]
			↑ PBMC GM-CSF secretion in children	[67]
			↑ Placental & cord blood IL-1β, TNF-α and IFN-γ in neonates	[79]
		Human cells	↑ Macrophage mRNA & secretion of TNF-α & IL-8	[130]
Lymphocyte activation	↓ Stimulated proliferation	Humans	PBMC in adults	[24–26]
			PBMC in children	[67]
		Animals	Chicken SMC & PBMC	[91]
			Mouse SMC	[92]
			Catfish SMC	[90, 93]
		Human cells	PBMC	[113, 114]
		Animal cells	Mouse SMC	[115, 116]
			Chicken SMC	[117]
	↓ Stimulated IL-2 secretion	Humans	PBMC in adults	[26]
			PBMC in children	[67]
		Animals	Mouse SMC	[92, 98]
			Catfish SMC	[93]
		Human cells	PBMC	[113, 114]
		Animal cells	Mouse SMC	[115, 116]
			Chicken SMC	[117]
			Harbor seal 11B7501 lymphoma B-cells	[118]
Humoral immunity	↓ AFC response to antigen	Animals	Mouse SMC	[89, 94–96]
			Rat SMC	[87, 97]
		Animal cells	Mouse SMC	[128, 129]
Hypersensitivity reaction	↓ Response to cutaneous sensitization	Animals	↓ LC migration to lymph nodes & subsequent T-cell activation in mice	[94, 99]
			Rats	[88, 100]
			Chickens	[91]
Monocytes/ macrophages	↓ Number/survival	Humans	↓ Monocyte count	[28]
		Animals	↓ Mouse splenic macrophage count	[89]
			↓ Catfish HK macrophage count	[90, 93]
			↑ Apoptosis of mouse splenic macrophages	[103]
		Human cells	↑ Apoptosis of blood monocytes & U937 promonocytic cells	[126]
	Impaired development	Human cells	↓ Differentiation of monocytes into macrophages	[130–133]
			Induced differentiation of macrophages into DC-like cells	[130, 131]
	Diminished function	Humans	Cell rounding; ↓ adhesion/CD54 adhesion molecule, F-actin, NO^- production & phagocytosis; altered Rho A-ROCK signaling	[29]
		Animals	↓ Rat PAM stimulated TNF-α secretion	[104]
			↓ Mouse peritoneal macrophage NO^- & O₂ ^- production	[101]
			↓ Mouse splenic macrophage adhesion, chemotactic index, phagocytosis, NO^- production, MHC class II surface expression & antigen presentation	[103, 105, 106]
			↓ Chicken SMC & PBMC NO^- production	[91]
			↓ Molluscan haemocyte phagocytosis & NO^- production	[102]
		Human cells	Cell rounding; ↓ adhesion & macrophage-specific markers; reorganized F-actin cytoskeleton resembling that of monocytes; ↑ monocytic marker CD14; ↓ endocytosis & phagocytosis via activated Rho A-ROCK signaling	[130, 131]
Survival	↑ Induction of apoptosis	Humans	PBMC in adults	[30]
			↑ PBMC BCL2L1 & CASP2 mRNA in adults	[22]
			PBMC in children	[64, 65]
			↑ CBMC CASP2 mRNA in neonates	[80]
		Animals	Mouse splenic macrophages	[103]
		Human cells	Blood monocytes & U937 promonocytic cells	[126]
			PBMC	[64]
			B-cells, T-cells, macrophages & neutrophils	[123]
		Animal cells	Mouse TA3 antigen-presenting B-cells	[125]
			Rat T-cells	[124]
ROS production	Induced oxidative stress	Humans	↑ Serum SOD & PBMC MDA in adults	[27]
			↑ Basal PBMC/monocyte NO^- & O₂ ^- in children	[72]
			↑ Placental 8-oxoguanine in neonates	[79]
			↑ Cord blood 8-hydroxy-2'-deoxyguanosine in neonates	[80]
	↓ Stimulated ROS production	Humans	↓ Macrophage NO^- in adults	[29]
			↓ Monocyte NO^- & O₂ ^- in children	[73]
		Animals	↓ Mouse peritoneal macrophage NO^- & O₂ ^-	[101]
			↓ Mouse splenic macrophage NO^-	[103, 105, 106]
			↓ Chicken SMC & PBMC NO^-	[91]
			↓ Molluscan haemocyte NO^-	[102]
			Zebrafish embryos & larvae	[84, 85]
Microbial challenge	↓ Clearance of pathogens	Animals	↑ Viral & bacterial loads in zebrafish embryos and larvae	[85]
			↑ Pathogen colonization & ulcers/septicemia following bacterial infection in catfish	[90, 93]
			↓ Splenic clearance of S. aureus in mice	[105]
			↑ Morbidity & respiratory viral titers following H1N1 viral infection in mice	[110]
Pulmonary health	Altered lung features	Humans	Altered airway protein expression in adults	[139, 141]
		Animals	Altered mouse airway protein expression	[140, 141]
			↓ Rat PAM stimulated TNF-α secretion	[104]
			↓ Mouse lung expression of genes involved in cell adhesion/migration	[81, 82]
			↓ Killifish gill chloride secretion via ↑ CFTR degradation	[136]
		Human cells	↓ CFBE41o- AE cell chloride secretion via ↑ CFTR degradation	[135]
			↓ 16HBE14o- bronchial epithelial cell migration and wound repair	[137, 138]
		Animal cells	↓ Rat PAM stimulated TNF-α secretion & NO^- & O₂ ^- production	[104]
	↑ Risk of infection/disease	Humans	↑ RTI & tuberculosis in adults	[26, 29, 35]
			↓ Lung function; ↑ prevalence/mortality from lung cancer and non-malignant lung disease, including bronchitis & bronchiectasis in adults	[34, 36–41]
			↑ RTI in infants	[77, 78]
		Animals	↑ Morbidity & respiratory viral titers following H1N1 infection in mice	[110]

Note: all cells are primary cells unless otherwise stated. Subjects of human studies are adults unless otherwise stated.
↓ decreased; ↑ increased.

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ISSN: 1476-069X

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