Eosinophil granule proteins increase microvascular macromolecular transport in the hamster cheek pouch
Minnicozzi, M.; Durán, W.N.; Gleich, G.J.; Egan, R.W.
Journal of Immunology 153(6): 2664-2670
1994
ISSN/ISBN: 0022-1767 PMID: 7521368 Document Number: 435682
By using microscopic, fluorometric, and immunologic methods, we have assessed the effects of eosinophil granule proteins on the microcirculation of the hamster cheek pouch. The plasma clearance of FITC-dextran 1 50 (FITC-dx 150) was used to quantify macromolecular transport. Topical application of major basic protein (MaBP) at 0.1 and 0.5 nM increased the clearance of FITC-dx 150 from a base line of 591 to 1 283 and 1966 nl/60 min/g, respectively. Numerous muscle fasciculations were also observed with the 0.5 nM dose of MaBP. Eosinophil cationic protein (ECP) was as potent as MaBP and caused an increase in the clearance of FITC-dx 150, 0.5 nM eliciting 21 56 nl/60 min/g. In contrast, topical application of 0.5 nM eosinophil peroxidase (EPO) increased clearance of FITC-dx 1 50 to a significantly lower level, 1113 nl/60 min/g. Supplementing 0.5 nM EPO with 1 nM H-2O-2 enhanced the clearance of FITC-dx 150 to 2404 nl/60 min/g, suggesting separate cationic charge and enzymatic activity-related effects. Compared with these eosinophil granule proteins, eosinophil-derived neurotoxin (EDN) required a 2000-fold higher concentration (1 mu-M) to elicit a significant increase in the clearance of FITC-dx 1 50 (I 505 nl/60 min/g). Neither EPO, EPO + H-2O-2, ECP, nor EDN at 1 mM caused muscle fasciculations. Quantitative analysis of the suffusates from the preparations exposed to these eosinophil proteins did not contain histamine. Our results demonstrate that MaBP, ECP, EPO, and EDN increase microvascular transport in the hamster cheek pouch and that this increase is independent of endogenous histamine release. The concentrations of eosinophil granule proteins causing increased vascular permeability are achieved in many pathologic conditions suggesting that the granule proteins play an important role in disease.