Polyarginine and eosinophil-derived major basic protein increase microvascular permeability independently of histamine or nitric oxide release.

Abstract

We tested the hypothesis that cationic peptides (polyarginine; poly-argn) and eosinophil-derived major basic protein (MaBP) increase permeability by stimulating the release of histamine and/or nitric oxide. We used intravital microscopy, clearance, and integrated optical intensity (IOI), using FITC-dextran 150 (FITC-dx 150) as a tracer, to evaluate changes in microvascular permeability in the hamster cheek pouch. Poly-argn at 1 microM (topical) increased the clearance of FITC-dx 150 from 610 to 3240 nl/60 min/g. In contrast, 1 microM polyglutamic acid (poly-glun; and anionic peptide) did not affect the clearance of FITC-dx 150 (605 nl/60 min/g). At 0.5 and 1.0 nM, poly-argn increased the clearance of FITC-dx 150 from 610 to 1722 and 2396 nl/60 min/g (P < 0.05). Similarly, 0.5 nM MaBP increased clearance from 591 +/- 38 to 1967 +/- 168 nl/60 min/g. L-NAME at 10(-4) M did not prevent the 0.5 nM MaBP-induced elevation in clearance (1784 +/- 350). Poly-argn at 1 nM increased net mean IOI by 21.5 +/- 7.2 units. This elevation was not inhibited by topical 10(-4) M L-NMMA (27.5 +/- 8.4). Using 0.5 nM poly-argn as agonist, we assayed suffusate samples for their histamine concentration using a competitive enzyme immunoassay and found no detectable histamine. Pyrilamine, an H1 antagonist, did not inhibit the 0.5 nM poly-argn-induced elevation in clearance of FITC-dx 150. We conclude that (1) cationic peptides and MaBP increase microvascular permeability and (2) the increase in microvascular permeability produced by low concentrations of poly-argn and by MaBP is independent of the release of histamine and does not require nitric oxide.