INCREASED HYALURONAN FLUX IN CANINE PAW LYMPH IS INDUCED BY HISTAMINEAND THE HISTAMINE-RELEASING AGENT COMPOUND-48 80/

The present experiments investigated hyaluronan (HYA) flux from skin o f pentobarbital anesthetized mongrel dogs when transcapillary fluid fl ux was increased by local intraarterial injection of histamine (50 mu g) or Compound 48/80 (C48/80) (100 mu g) inducing mast cell degranulat ion. A prenodal lymphatic draining the hindpaw was cannulated and the paw flexed passively at 50 times/min. Grand mean (n = 18) of control l ymph flow and HYA concentration was 16 +/- (SD) 14 mu l/min and 8.8 +/ - 2.3 mu g/ml, respectively. Lymph flow increased 11- and 15-fold with in 10 min after histamine and C48/80 injection, respectively, and retu rned 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 ve hicle) showed an unexpected and gradual increase in HYA concentration during the 8-hour experimental period, regardless of unchanged lymph f low. This increase became statistically significant at the end of the experimental period, suggesting either an increased synthesis or incre ased rate of release of bound HYA from the paw. The present data show that HYA is loosely bound and easily mobilized from the interstitial m atrix 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 syn thesis of HYA.