A NOVEL PHYSIOLOGICAL-FUNCTION FOR PLATELET-DERIVED GROWTH FACTOR-BB IN RAT DERMIS

1. The present experiments describe a role for platelet-derived growth factor-BE and cellular adhesion receptors towards extracellular matri x molecules (beta(1)-integrins) in control of interstitial fluid press ure (P-if). 2. P-if was measured in rat skin with sharpened glass capi llaries (3-7 mu m) connected to a servocontrolled counter-pressure sys tem. 3. The collagen and laminin-binding alpha(2) beta(1)-integrin is involved in the control of P-if since subdermal injection (5 mu l) of monoclonal hamster anti-rat alpha(2) beta(1)-integrin IgG (anti-alpha( 2) beta(1)) resulted in increased negativity of P-if. Control P-if ave raged -0.88 +/- 0.23 mmHg (+/- S.D.) and decreased to -2.50 +/- 0.35 m mHg (P < 0.05) and -3.88 +/- 1.45 mmHg (P < 0.05) at anti-alpha(2) bet a(1) concentrations of 0.56 and 1.12 mg ml(-1), respectively. 4. The e ffect of anti-alpha(2) beta(1) was abolished when platelet-derived gro wth factor-BE (PDGP-BB) (200 ng ml(-1)) mras injected together with an ti-alpha(2) beta(1). 5. The time- and dose-responses of PDGF-BB to cou nteract increased negativity of P-if were studied further using dextra n anaphylaxis as an experimental model inducing increased negativity o f P-if in shin. Control P-if averaged -0.33 +/- 0.43 mmHg and fell to -4.10 +/- 1.47 mmHg within 10 min after dextran (P<0.01). Subsequent s ubdermal injection of PDGF-BB at 200 ng ml(-1) normalized P-if in 10-2 0 min which became -1.37 +/- 1.23 mmHg (P < 0.01 versus dextran, P > 0 .05 versus control). PDGF-BB had little or no effect at 50 ng ml(-1). PDGF-AA and basic fibroblast growth factor had no effect on P-if. 6. T he in vivo function reported for PDGF-BB has not)seen described previo usly and provides further evidence for active participation of connect ive tissue cells in control of P-if by altering tension on extracellul ar matrix structures.