Table 1.
Functional studies of signaling molecules in carbon nanotube (CNT)-induced pulmonary immune responses using knockout (KO) mice.
| KO mice | CNTs | Effects | Findings in KO mice | References |
|---|---|---|---|---|
| IL-1R KO | long, rod-like MWCNTs (XNRI MWNT-7) OD: >50 nm L: ~13 µm long, tangled MWCNTs OD: 8–15 nm L: 10–50 µm |
acute inflammation | Long, rod-like MWCNTs, but not long, tangled MWCNTs, increase neutrophils in BAL and pro-inflammatory cytokine and chemokine expression in lung tissues 16 h post-exposure in WT mice, which are attenuated in IL-1R KO mice. Long, rod-like MWCNTs induce Th2-type inflammation on day 28 post-exposure in WT mice, which is not affected in IL-1R KO mice. |
(29) |
| IL-1R KO | MWCNTs (XNRI MWNT-7) D: 49±13.4 nm L: 3.86±1.94 µm |
acute inflammation | MWCNT-induced acute inflammation is suppressed in IL-1R KO mice 24 h post-exposure, compared with WT mice, whereas IL-1R KO does not suppress inflammation on day 28 post-exposure, determined by the numbers of total cells, mononuclear cells, and neutrophils and the levels of IL-6, IL-12p40, and CXCL1 in BAL. | (30) |
| caspase-1 KO | MWCNTs (FA-21) D: 27 nm L: 5–15 µm |
acute inflammation | The level of IL-1β, the number of total cells, and the number of neutrophils in BAL are significantly increased by MWCNTs on day 1 post-exposure in WT mice, but not in caspase-1 KO mice. The number of eosinophils in BAL is significantly increased by MWCNTs on day 1 post-exposure in WT mice, which is not affected in caspase-1 KO mice. |
(31) |
| ST2 KO | MWCNTs D: 22.5±1.3 nm L: 10–100 µm |
chronic inflammation type 2 immune response |
The induction of inflammation, fibrosis, and functional damage by MWCNTs in the lung on day 30 post-exposure is inhibited in mast cell-deficient KitW-sh mice and ST2 KO mice, compared with WT mice. Reconstitution of KitW-sh mice with WT BMMCs restores these MWCNT-induced pathological outcomes, whereas that with ST2 KO BMMCs does not. | (32) |
| IL-13 KO | MWCNTs (FA-21) D: 27 nm L: 5–15 µm |
type 2 immune response | MWCNTs increase eosinophils in WLL 24 h post-exposure in WT mice, but not in IL-13 KO mice. | (33) |
| IL-33 KO | MWCNTs (FA-21) D: 27 nm L: 5–15 µm |
type 2 immune response | MWCNTs increase eosinophils in WLL 24 h post-exposure in WT mice, but not in IL-33 KO mice. | (33) |
| IL-33 KO | MWCNTs D: 22.5±1.3 nm L: 10–100 µm |
chronic inflammation type 2 immune response |
The number of eosinophils in BAL is increased by MWCNTs on day 30 post-exposure in WT mice, which is attenuated in IL-33 KO mice. MWCNTs induce fibrosis near the airways in WT mice, but not in IL-33 KO mice, on day 30 post-exposure. |
(34) |
| STAT6 KO | MWCNTs (XNRI MWNT-7) D: 49±13.4 nm L: 3.86±1.94 µm |
type 2 immune response | The level of IL-5 is elevated by MWCNTs in the BAL from WT mice, but not in the BAL from STAT6 KO mice, 24 h post-exposure. MWCNT-induced fibrotic phenotype is weakened in STAT6 KO lung tissues, compared with WT lung tissues, on day 28 post-exposure. |
(30) |
D, diameter; L, length; OD, outside diameter; WLL, whole lung lavage.