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 (/1-integrins) in control of interstitial fluid pressure (Pif). and decreased to -2-50 + 0 35 mmHg (P < 0 05) and -3-88 + 1P45 mmHg (P < 0 05) at anti-a2/11 concentrations of 0-56 and 1P12 mg ml-', respectively.4. The effect of anti-a0231 was abolished when platelet-derived growth factor-BB (PDGF-BB) (200 ng ml-') was injected together with anti-ca2/1. 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 + 0A43 mmHg and fell to -4-10 + 1P47 mmHg within 10 min after dextran (P < 0-01). Subsequent subdermal injection of PDGF-BB at 200 ng ml-' 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-. 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.During the initial stage of several acute inflammatory reactions, loose connective tissues will 'actively' enhance transcapillary fluid flux and oedema formation in skin and airways, since an increased negativity of interstitial fluid pressure (Pif) from -1 to between -5 and -10 inmHg will provide an increased driving pressure for fluid filtration

A simple method for measuring interstitial fluid pressure in cancer tissues

“…In this respect, it is also noteworthy that pericytes are known to control interstitial pressure (IFP) by regulating their attachment to a collagen/microfibrillar network, which in turn restrains a proteoglycan/hyaluronan gel from retaining water (Pietras et al, 2001;Heldin et al, 2004;Rodt et al, 1996). In addition, signaling through PDGF β-receptors on pericytes increases IFP, whereas its inhibition reduces IFP (Pietras et al, 2001).…”

Targeting Microvascular Pericytes in Angiogenic Vessels of Prostate Cancer

“…In this respect, it is also noteworthy that pericytes are known to control interstitial pressure (IFP) by regulating their attachment to a collagen/microfibrillar network, which in turn restrains a proteoglycan/hyaluronan gel from retaining water (Pietras et al, 2001;Heldin et al, 2004;Rodt et al, 1996). In addition, signaling through PDGF hreceptors on pericytes increases IFP, whereas its inhibition reduces IFP (Pietras et al, 2001).…”

“…Cancer cells are therefore exposed to a lower effective concentration of therapeutic agents than normal cells, reducing treatment efficiency. Decreasing tumor IFP can thus improve convection of cancer chemotherapeutics into the tumor (Jain, 1987a,b;Heldin et al, 2004).In this respect, it is also noteworthy that pericytes are known to control interstitial pressure (IFP) by regulating their attachment to a collagen/microfibrillar network, which in turn restrains a proteoglycan/hyaluronan gel from retaining water (Pietras et al, 2001;Heldin et al, 2004;Rodt et al, 1996). In addition, signaling through PDGF hreceptors on pericytes increases IFP, whereas its inhibition reduces IFP (Pietras et al, 2001).…”

Development and possible clinical use of antagonists for PDGF and TGF-β

“…The importance of PDGF for the connective tissue compartment is also illustrated by the fact that PDGF regulates the interstitial fluid pressure (10). The exact mechanism involved is not known, but probably involves increased interactions between fibroblasts of the connective tissue and matrix molecules, and a stimulation of contraction of fibroblasts through effects on the actin filament system of such cells.…”