COLLAGEN INDUCES CYTOKINE RELEASE BY FETAL PLATELETS - IMPLICATIONS IN SCARLESS HEALING

In previous studies the authors demonstrated that unlike adult platele ts, fetal platelets respond poorly to collagen. When platelets make co ntact with the exposed collagen at the site of injury, the result is a ctivation, aggregation, and degranulation with the release of cytokine s and growth factors. This sequence of events is well characterized in adult wounds, which heal with an acute inflammatory response and dens e 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, abunda nt at the site of dermal injury, is a poor inducer of cytokine release by fetal platelets. This could explain, in part, the minimal inflamma tion accompanying fetal dermal wound healing. Platelet suspensions fro m six fetal Yorkshire swine at day 80 of gestation (term, 114 days) we re exposed to either arachidonic acid, 0.5 mg/mL, collagen, 0.19 mg/mL , or saline. The release into plasma of transforming growth factor-bet a (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 bioch emical findings with ultrastructural changes and showed that arachidon ate-treated platelets were aggregated and devoid of granules. In contr ast, collagen-treated platelets had undergone conformational changes b ut showed only a moderate change in the quantity and homogeneity of th eir secretory granules compared with saline-treated controls. There wa s a significant increase in TGF-beta 1 release into plasma after treat ment 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 wi th saline (0.09 +/- 0.02 ng/ml), P <.05. The authors conclude that fet al 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 w ounding. Copyright (C) 1997 by W.B. Saunders Company.