High and Low Molecular Weight Hyaluronic Acid Differentially Regulate Human Fibrocyte Differentiation

Following tissue injury, monocytes can enter the tissue and differentiate into fibroblast-like cells called fibrocytes, but little is known about what regulates this differentiation. Extracellular matrix contains high molecular weight hyaluronic acid (HMWHA; ∼2×10(6) Da). During injury, HMWHA breaks down to low molecular weight hyaluronic acid (LMWHA; ∼0.8-8×10(5) Da).In this report, we show that HMWHA potentiates the differentiation of human monocytes into fibrocytes, while LMWHA inhibits fibrocyte differentiation. Digestion of HMWHA with hyaluronidase produces small hyaluronic acid fragments, and these fragments inhibit fibrocyte differentiation. Monocytes internalize HMWHA and LMWHA equally well, suggesting that the opposing effects on fibrocyte differentiation are not due to differential internalization of HMWHA or LMWHA. Adding HMWHA to PBMC does not appear to affect the levels of the hyaluronic acid receptor CD44, whereas adding LMWHA decreases CD44 levels. The addition of anti-CD44 antibodies potentiates fibrocyte differentiation, suggesting that CD44 mediates at least some of the effect of hyaluronic acid on fibrocyte differentiation. The fibrocyte differentiation-inhibiting factor serum amyloid P (SAP) inhibits HMWHA-induced fibrocyte differentiation and potentiates LMWHA-induced inhibition. Conversely, LMWHA inhibits the ability of HMWHA, interleukin-4 (IL-4), or interleukin-13 (IL-13) to promote fibrocyte differentiation.We hypothesize that hyaluronic acid signals at least in part through CD44 to regulate fibrocyte differentiation, with a dominance hierarchy of SAP>LMWHA≥HMWHA>IL-4 or IL-13

Micronutrient, antioxidant, and oxidative stress status in children with severe cerebral palsy

Background: Markers indicative of micronutrient and antioxidant status in children with cerebral palsy (CP) were explored due to these children's well-documented issues with food intake and the limited biochemical literature. Materials and Methods: Children aged 4 to 12 years with marked CP (n = 24) and controls (n = 24) were recruited. The CP group represented orally (O) or enterally fed (E) children. Concentrations of red cell folate (RCF), magnesium, superoxide dismutase (SOD), glutathione reductase, and peroxidase were measured, as well as serum methylmalonic acid and vitamin C. Plasma hemoglobin, C-reactive protein, alpha-tocopherol, cholesterol, zinc, protein carbonyls, and total antioxidant capacity were also quantified. Results: Data are reported as mean (SD) and z scores where values differ with age. Many similarities existed, but zinc z scores were reduced in O (-1.10 [0.83]) vs controls (-0.54 [0.54]) (P < .05), as well as for glutathione reductase in O (10.15 [1.69]) vs E (12.22 [2.41]) and controls (11.51 [1.67]) (P < .05). RCF was greatly increased in E (1422 [70]) vs O (843 [80]) and controls (820 [43]) (P < .001). SOD was decreased in E (24.3 [1.4]) vs controls (27.0 [2.8]) (P < .05). Conclusion: Considering their vast impact on physiology, micronutrients should be routinely monitored in orally fed children with swallowing disorders and dietary limitations. Excessive intakes, particularly long term in enterally fed children, should also be monitored in view of their potential for competitive inhibition, particularly at high levels. (JPEN J Parenter Enteral Nutr. 2013;37:97-101