title: A novel physiological function for platelet-derived growth factor-BB in rat dermis.
abstract: 1. The present experiments describe a role for platelet-derived growth factor-BB and cellular adhesion receptors towards extracellular matrix molecules (beta 1-integrins) in control of interstitial fluid pressure (Pif). 2. Pif was measured in rat skin with sharpened glass capillaries (3-7 microns) connected to a servocontrolled counter-pressure system. 3. The collagen and laminin-binding alpha 2 beta 1-integrin is involved in the control of Pif since subdermal injection (5 microliters) of monoclonal hamster anti-rat alpha 2 beta 1-integrin IgG (anti-alpha 2 beta 1) resulted in increased negativity of Pif. Control Pif averaged -0.88 +/- 0.23 mmHg (+/- S.D.) and decreased to -2.50 +/- 0.35 mmHg (P < 0.05) and -3.88 +/- 1.45 mmHg (P < 0.05) at anti-alpha 2 beta 1 concentrations of 0.56 and 1.12 mg ml-1, respectively. 4. The effect of anti-alpha 2 beta 1 was abolished when platelet-derived growth factor-BB (PDGF-BB) (200 ng ml-1) was injected together with anti-alpha 2 beta 1. 5. The time- and dose-responses of PDGF-BB to counteract increased negativity of Pif were studied further using dextran anaphylaxis as an experimental model inducing increased negativity of Pif in skin. Control Pif averaged -0.33 +/- 0.43 mmHg and fell to -4.10 +/- 1.47 mmHg within 10 min after dextran (P < 0.01). Subsequent subdermal injection of PDGF-BB at 200 ng ml-1 normalized Pif in 10-20 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 Pif. 6. The in vivo function reported for PDGF-BB has not been described previously and provides further evidence for active participation of connective tissue cells in control of Pif by altering tension on extracellular matrix structures.
authors.affiliation: Department of Medical and Physiological Chemistry, University of Uppsala, Sweden.
authors.forename: S A
authors.initials: SA
authors.lastname: Rodt
authors.forename: K
authors.initials: K
authors.lastname: Ahlén
authors.forename: A
authors.initials: A
authors.lastname: Berg
authors.forename: K
authors.initials: K
authors.lastname: Rubin
authors.forename: R K
authors.initials: RK
authors.lastname: Reed
mesh_terms: D000818:Animals; D000077214:Becaplermin; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005260:Female; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology / Q000502:physiology*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017208:Rats, Wistar; D012879:Skin Physiological Phenomena
chemical_list: D006133:Growth Substances; D016023:Integrins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin