Hyaluronic acid inhibits fetal platelet function: implications in scarless healing.
Platelets are important for the initiation of inflammation in adults, but the role of fetal platelets in fetal wound healing is unclear because fetal dermal wounds heal with a minimal inflammatory response and lack of excessive scarring. Because fetal tissue is abundant in glycosaminoglycans (GAGs), predominantly hyaluronic acid (HA), this study was designed to test the hypothesis that HA inhibits the reactivity of platelets and thus contributes to the minimal scarring characteristic of fetal tissue repair. Platelets were isolated from 10 fetal pigs at day 80 of gestation (term, 115 days) and exposed to 0.5 mg/mL of arachidonic acid, an agent shown in prior studies to evoke maximal aggregation and degranulation of fetal platelets. The ability of HA at 0.1 and 0.5 mg/mL to inhibit this response was determined. The presence of HA resulted in a dose-dependent reduction in platelet aggregation at 180 seconds (control, 99.7 +/- 0.3%; HA [0.1 mg/mL] 91.7 +/- 3.8%; and HA [0.5 mg/mL] 48.5 +/- 9.0%; P < .005 v control). The onset of aggregation was also significantly delayed by 0.5 mg/mL of HA (13.5 +/- 2.5 seconds) compared to control (2.9 +/- 0.7 seconds), P < .05. No significant diminution of platelet aggregation could be achieved by the addition of other GAGs at similar concentrations. HA also significantly impaired the release of platelet-derived growth factor (PDGF)-AB from fetal platelets. The authors conclude that HA, the predominant GAG in fetal dermal matrix, inhibits platelet aggregation and cytokine release. This inhibition of platelet aggregation and resultant inflammatory response may explain, in part, the minimal inflammation and scarless healing characteristic of fetal dermal repair.
Olutoye
O O
OO
The Wound Healing Center, Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0117, USA.
Barone
E J
EJ
Yager
D R
DR
Uchida
T
T
Cohen
I K
IK
Diegelmann
R F
RF
D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005312:Fetal Blood / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000494:pharmacology; D006820:Hyaluronic Acid / Q000494:pharmacology*; D007249:Inflammation / Q000503:physiopathology; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D013552:Swine; D014945:Wound Healing / Q000502:physiology*
D006025:Glycosaminoglycans; D010975:Platelet Aggregation Inhibitors; D010982:Platelet-Derived Growth Factor; C095477:platelet-derived growth factor AB; D006820:Hyaluronic Acid