Blockade of beta 1-integrins in skin causes edema through lowering of interstitial fluid pressure.
The increased capillary fluid filtration required to rapidly create edema in acute inflammation can be generated by increased negativity of the interstitial fluid pressure (Pif). This observation suggests that connective tissues can "actively" enhance capillary fluid filtration. We now show that in vivo blockade of beta 1-integrin adhesion receptors in rat skin causes local edema concomitant with increased negativity of Pif. Experiments were performed on the dorsal side of the hind paw, and Pif was measured with sharpened glass capillaries (tip diameter, 3-7 microns) connected to a servo-controlled counterpressure system. Measurements were made after circulatory arrest had been induced with intracardiac potassium chloride in pentobarbital anesthesia. This procedure prevents the vascular phenomena of increased fluid and protein flux leading to edema formation, which in turn can increase Pif and therefore potentially mask an increased negativity of Pif. Control Pif averaged -0.58 +/- 0.81 (mean +/- SD) mm Hg (n = 37). Subdermal injection of 5 microliters monospecific rabbit anti-rat integrin beta 1-subunit immunoglobulin G caused increased negativity of Pif to average values between -4 and -6 mm Hg within 10 minutes after injection. Subdermal injection of 0.9% NaCl, preimmune immunoglobulin G, rat anti-fibronectin, and peptides with Arg-Gly-Asp and Arg-Gly-Glu sequences did not change Pif significantly. In another series of experiments, 5 microliters anti-beta 1 integrin immunoglobulin G was injected subdermally in rats with intact circulation and resulted in an increase in total tissue water corresponding to a doubling of the interstitial fluid volume in 10 minutes (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Reed
R K
RK
Department of Physiology, University of Bergen, Norway.
Rubin
K
K
Wiig
H
H
Rodt
S A
SA
D000208:Acute Disease; D000818:Animals; D001826:Body Fluids / Q000502:physiology*; D002196:Capillaries / Q000502:physiology; D004487:Edema / Q000209:etiology*; D005260:Female; D007074:Immunoglobulin G / Q000008:administration & dosage*; D007249:Inflammation; D016023:Integrins / Q000037:antagonists & inhibitors / Q000502:physiology*; D011312:Pressure; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012879:Skin Physiological Phenomena; D013997:Time Factors
D007074:Immunoglobulin G; D016023:Integrins