MICROVASCULAR PRESSURE AND ALBUMIN EXTRAVASATION AFTER LEUKOCYTE ACTIVATION IN HAMSTER-CHEEK POUCH

The effects of leukotriene B4 (LTB4) and N-formyl-methionyl-leucylphenylalanine (FMLP) on transmicrovascular exchange of fluorescein isothiocyanate (FITC)-labeled serum albumin and dextran (molecular mass, 150,000 Da) were evaluated in hamster cheek pouch utilizing measurements of microvascular pressure and global efflux of the macromolecular markers into the tissue suffusate. Exposure of the suffused pouch to 1.0 muM LTB4 failed to alter microvascular pressure from its control level. The microvascular clearance of FITC-albumin rose to a peak value of 1.7 times the control value at a LTB4 concentration of 1.0 muM; the rate of albumin extravasation did not change from the normal level at a concentration of 0.1 muM. The extravasation rate of FITC-dextran was elevated with both doses of LTB4; the leukocyte chemotactic agent elicited 2.4- and 9.7- fold increments in peak clearance of dextran at concentrations of 0.1 and 1.0 muM, respectively. FMLP elicited a twofold increase in venular and terminal arteriolar pressures at a concentration of 1 muM; at the same concentration, the albumin clearance rose 3.5-fold. The results suggest that albumin transport remains near the normal level after LTB4 elicits massive migration of leukocytes across the venular membrane. By contrast, albumin transport is greatly accelerated following exposure to the chemotactic peptide FMLP; ultrastructural and physiological evidence suggests that the leakage of albumin is augmented by increases in microvascular permeability and filtration pressure. The results also reinforce previous ultrastructural observations from our laboratory indicating that diapedesis per se is not a cause of microvascular hyperpermeability in inflammatory reactions.