Macrophages Modulated by Red/NIR Light: Phagocytosis, Cytokines, Mitochondrial Activity, Ca²⁺ Influx, Membrane Depolarization and Viability

Abstract

Low-level light therapy (LLLT) is emerging as a promising therapeutic approach to modulate the biochemical and molecular processes within living cells. LLLT is known to produce local and systemic effects; therefore, immune cells in local tissues or in the circulation are affected by light. However, this specific effect remains weakly explored. In this study, the effect of red (650 nm) and NIR (808 nm) light on phagocytosis (respiratory burst), cytokine expression, mitochondrial activity, ROS generation, Ca 2+ influx and membrane depolarization in macrophages in vitro is investigated. Both the phagocytic capacity and adhesion of macrophages strongly (~2.5 times) increased in the first hours after exposure to light in a dose-dependent manner. The light-evoked upregulation of phagocytosis is found to be less efficient than the maximal pharmacologically induced enhancement of ~3.2 times. Also, red/NIR light reduces the production of pro-inflammatory cytokines and activates the secretion of anti-inflammatory cytokines by several times in activated macrophages. At the same time, the viability shows a biphasic dose response: it increases after irradiation with lower doses (0.3-1 J cm À2 ) and decreases after treatment with higher doses (18-30 J cm À2 ), which is apparently associated with the upregulation of ROS generation, followed by an increase in the mitochondrial activity.

Comparing the Impact of NIR, Visible and UV Light on ROS Upregulation via Photoacceptors of Mitochondrial Complexes in Normal, Immune and Cancer Cells

“…HeLa and 4T1 cancer cells show slow linear-like rising dynamics of ROS generation, but the ROS level after 10 min becomes higher than in other cells: by 38 and 26% in HeLa cells and by 39 and 30% in 4T1 cells under 650 and 808 nm light, respectively. In our experiments, comparing red and NIR light at the same intensity, it can be argued that light of 650 nm wavelength more efficiently stimulates mitochondrial ETC and subsequent ROS generation than 808 nm, which is consistent with literature data (3,4,28,58).…”

“…Figure 1 shows the effect of light of 375/450/530/650/808/1064 nm wavelengths at various power densities from 10 to 300 mW cm À2 (for 1064 nm light from 0.1 to 2 W cm À2 ) on ROS generation in the neuroblastoma model. These light power densities and doses have been chosen because red/NIR PBM with commonly used parameters (10-100 mW cm À2 , ~0.1-30 J cm À2 ) provides positive effects on tissues and cells without inhibiting their viability, while light at power densities higher than 100 mW cm À2 and doses higher than ~10 J cm À2 may be unsafe for tissue cells causing nonthermal cell phototoxicity (3,4,28,(48)(49)(50)(51)(52)(53)(54). So, we investigate the influence of so-called low-intensity light below 100 mW cm À2 and irradiation with higher intensities above this edge, in which neither causes heating.…”

“…To date, the most discussed photoacceptor is cytochrome c oxidase (CCO) (6,13). CCO absorbs red/NIR light within wavelengths ranging between 600 and 1000 nm, resulting in the activation of metabolic process as well as migration and proliferation of various cell types: neurons (650–660/808 nm at 3–90 J cm −2 (3,4,14), fibroblasts (660 nm at 5 J cm −2 (15), 660 nm at 3–8 J cm −2 (16), 809 nm at 1.96–7.84 J cm −2 (17)), endothelial cells (635 nm at 24 J cm −2 (18), 650 nm at 30 J cm −2 (19), 665 and 675 nm at 10 J cm −2 (20), 808 nm at 60 J cm −2 (21)), stem cells (660 nm (22,23) and 808 nm at 3 J cm −2 (24)), keratinocytes (780 nm at 0.45–0.95 J cm −2 (25)), lymphocytes (660 nm at 0–5.0 J cm −2 (26), 820 nm at 1.2–8.4 J cm −2 (27)), macrophages (650/808 nm at 3–90 J cm −2 (28)), cancer cells (650/808 nm at 3–90 J cm −2 (3,4), 830 nm at 2 J cm −2 (29)), rat pre‐odontoblast cells (980 nm at 0.65–6.5 J cm −2 (30)), rat satellite cells (632.8 nm at 0.18 J cm −2 (31)), myoblast cells (808 nm at 10–70 J cm −2 (32)) and other cells (33–35).…”

Therapeutic Potential of Photobiomodulation for Chronic Kidney Disease

“…A recent study further confirmed the anti-inflammatory effect of PBM on macrophages collected from male mice with reduced pro-inflammatory cytokines and increased anti-inflammatory cytokines. Interestingly, the biphasic dose-response was observed in cell viability, which was increased at a lower dosage but decreased at a higher dosage [ 105 ].…”

Long wavelength light that improves aged mitochondrial function selectively increases cytokine expression in serum and the retina

“…There is limited evidence that longer wavelength exposure also impacts on immunity [11][12][13] . However, this remains relatively unexplored.…”