Lower cytokine release by fetal porcine platelets: A possible explanation for reduced inflammation after fetal wounding

Abstract

Fetal dermal wound healing is unique because of its rapidity, minimal inflammation, and lack of scarring. Cytokines such as transforming growth factor beta (TGF-β) and platelet-derived growth factor (PDGF) evoke an inflammatory response and scarring when applied to fetal wounds. Because adult and fetal platelet counts are comparable, the aim of this study was to test the hypothesis that the minimal inflammatory response seen in the fetus is attributable to differences in the serum content of cytokines released by fetal platelets. Using Yorkshire swine, blood was collected from 10 adults and 10 fetuses at day 60 of gestation (fullterm, 114 days). Platelets were isolated from anticoagulated blood and examined by transmission electron microscopy. Serum was analyzed for PDGF-AB and TGF-β2 by enzyme-linked immunosorbent assay (ELISA), and TGF-β1 by 125I radioimmunonoassay. TGF-β samples were assayed with and without prior acid activation to determine the total TGF-β and the biologically active form of the cytokine. Electron microscopy of adult and fetal platelets showed no gross structural differences. Alpha granules, which contain cytokines as well as procoagulant factors, were present in similar quantities and with the same degree of homogeneity. The cytokines analyzed were present in all the adult and fetal sera tested. However, PDGF-AB was present in significantly lower concentrations in the fetus (383 ± 72 pg/mL v 972 ± 185 pg/mL in the adult; P < .05). In addition, the fetal samples contained lower amounts of TGF-β1 (13,895 ± 1,770 v 29,864 ± 5,050 pg/mL; P < .05) and TGF-β2 (6,758 ± 734 v 13,407 ± 1,395 pg/mL; P < .05). The majority of TGF-β was in latent form; the adult sera contained significantly more active TGF-β1 and active TGF-β2 than the fetal sera. The ratios of active TGF-β1 to active TGF-β2 were similar for the adult (22.3) and fetus (18.5). However the ratio of total TGF-β1 to total TGF-β 2 was significantly lower for the fetus (2.26 v 7.69). The authors conclude that although no gross differences in platelet ultrastructure were noted, fetal porcine platelets release lower quantities of cytokines into serum. This lower serum cytokine content and the relative concentrations of TGF-β1 and TGF-β2 may explain, in part, the minimal inflammation and sparse fibrosis characteristic of fetal wounds. These observations provide further insight into the unique fetal response to wounding and may offer alternative avenues to modulate the postnatal wound healing response.