EOSINOPHIL GRANULE PROTEINS INCREASE MICROVASCULAR MACROMOLECULAR TRANSPORT IN THE HAMSTER-CHEEK POUCH

By using microscopic, fluorometric, and immunologic methods, we have a ssessed the effects of eosinophil granule proteins on the microcircula tion of the hamster cheek pouch. The plasma clearance of FITC-dextran 150 (FITC-dx 150) was used to quantify macromolecular transport. Topic al application of major basic protein (MaBP) at 0.1 and 0.5 nM increas ed the clearance of FITC-dx 150 from a base line of 591 to 1283 and 19 66 nl/60 min/g, respectively. Numerous muscle fasciculations were also observed with the 0.5 nM dose of MaBP. Eosinophil cationic protein (E CP) was as potent as MaBP and caused an increase in the clearance of F ITC-dx 150, 0.5 nM eliciting 2156 nl/60 min/g. in contrast, topical ap plication of 0.5 nM eosinophil peroxidase (EPO) increased clearance of FITC-dx 150 to a significantly lower level, 1113 nl/60 min/g. Supplem enting 0.5 nM EPO with 1 nM H2O2 enhanced the clearance of FITC-dx 150 to 2404 nl/60 min/g, suggesting separate cationic charge and enzymati c activity-related effects. Compared with these eosinophil granule pro teins, eosinophil-derived neurotoxin (EDN) required a 2000-fold higher concentration (1 mu M) to elicit a significant increase in the cleara nce of FITC-dx 150 (1505 nl/60 min/g). Neither EPO, EPO + H2O2, ECP, n or EDN at 1 mM caused muscle fasciculations. Quantitative analysis of the suffusates from the preparations exposed to these eosinophil prote ins did not contain histamine. Our results demonstrate that MaBP, ECP, EPO, and EDN increase microvascular transport in the hamster cheek po uch and that this increase is independent of endogenous histamine rele ase. The concentrations of eosinophil granule proteins causing increas ed vascular permeability are achieved in many pathologic conditions su ggesting that the granule proteins play an important role in disease.