Increased hyaluronan flux in canine paw lymph is induced by histamine and the histamine-releasing agent compound 48/80.

The present experiments investigated hyaluronan (HYA) flux from skin of pentobarbital anesthetized mongrel dogs when transcapillary fluid flux was increased by local intraarterial injection of histamine (50 micrograms) or Compound 48/80 (C48/80) (100 micrograms) inducing mast cell degranulation. A prenodal lymphatic draining the hindpaw was cannulated and the paw flexed passively at 50 times/min. Grand mean (n = 18) of control lymph flow and HYA concentration was 16 +/- (SD) 14 microliters/min and 8.8 +/- 2.3 micrograms/ml, respectively. Lymph flow increased 11- and 15-fold within 10 min after histamine and C48/80 injection, respectively, and returned to control values after 3 h for histamine while it did not return fully in the C48/80 group. HYA concentration decreased by 30 and 40% during the first hour after histamine and C48/80, respectively, while HYA flux increased 11-15 times control. Control experiments (saline vehicle) showed an unexpected and gradual increase in HYA concentration during the 8-hour experimental period, regardless of unchanged lymph flow. This increase became statistically significant at the end of the experimental period, suggesting either an increased synthesis or increased rate of release of bound HYA from the paw. The present data show that HYA is loosely bound and easily mobilized from the interstitial matrix and that histamine and C48/80 cause a release of bound HYA from the interstitium. An increase in HYA concentration towards the end of the 8-hour experimental period most likely represents an increased synthesis of HYA.