title: Collagen induces cytokine release by fetal platelets: implications in scarless healing.
abstract: In previous studies the authors demonstrated that unlike adult platelets, fetal platelets respond poorly to collagen. When platelets make contact with the exposed collagen at the site of injury, the result is activation, aggregation, and degranulation with the release of cytokines and growth factors. This sequence of events is well characterized in adult wounds, which heal with an acute inflammatory response and dense scar formation. In sharp contrast, fetal dermal wounds heal without an acute inflammatory response and minimal scar formation. Therefore, the aim of this study was to test the hypothesis that collagen, abundant at the site of dermal injury, is a poor inducer of cytokine release by fetal platelets. This could explain, in part, the minimal inflammation accompanying fetal dermal wound healing. Platelet suspensions from six fetal Yorkshire swine at day 80 of gestation (term, 114 days) were exposed to either arachidonic acid, 0.5 mg/mL, collagen, 0.19 mg/mL, or saline. The release into plasma of transforming growth factor-beta (TGF-beta 1), and platelet-derived growth factor (PDGF)-AB effected by these agents was determined by enzyme-linked immunosorbent assays. Transmission electron microscopy (TEM) was used to correlate the biochemical findings with ultrastructural changes and showed that arachidonate-treated platelets were aggregated and devoid of granules. In contrast, collagen-treated platelets had undergone conformational changes but showed only a moderate change in the quantity and homogeneity of their secretory granules compared with saline-treated controls. There was a significant increase in TGF-beta 1 release into plasma after treatment with collagen (6.64 +/- 0.36 ng/mL) and arachidonate (7.64 +/- 0.77 ng/mL) compared with saline (4.74 +/- 0.36 ng/mL), P < .05. Likewise, PDGF-AB release was significantly higher after collagen (0.22 +/- 0.02 ng/mL) and arachidonate treatment (0.44 +/- 0.04 ng/mL) compared with saline (0.09 +/- 0.02 ng/ mL), P < .05. The authors conclude that fetal platelets actually do release cytokines in response to contact with collagen despite poor aggregation. Therefore, impaired aggregation to collagen cannot solely explain the minimal inflammation after fetal wounding.
authors.affiliation: Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0117, USA.
authors.forename: O O
authors.initials: OO
authors.lastname: Olutoye
authors.forename: E J
authors.initials: EJ
authors.lastname: Barone
authors.forename: D R
authors.initials: DR
authors.lastname: Yager
authors.forename: I K
authors.initials: IK
authors.lastname: Cohen
authors.forename: R F
authors.initials: RF
authors.lastname: Diegelmann
mesh_terms: D000818:Animals; D002921:Cicatrix / Q000503:physiopathology; D003094:Collagen / Q000494:pharmacology*; D004195:Disease Models, Animal; D005312:Fetal Blood / Q000502:physiology*; D008854:Microscopy, Electron; D010974:Platelet Aggregation / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D013552:Swine; D016212:Transforming Growth Factor beta / Q000097:blood*; D014945:Wound Healing / Q000502:physiology*
chemical_list: D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; C095477:platelet-derived growth factor AB; D003094:Collagen