POLYARGININE AND EOSINOPHIL-DERIVED MAJOR BASIC-PROTEIN INCREASE MICROVASCULAR PERMEABILITY INDEPENDENTLY OF HISTAMINE OR NITRIC-OXIDE RELEASE

We tested the hypothesis that cationic peptides (polyarginine; poly-ar g(n)) and eosinophil-derived major basic protein (MaBP) increase perme ability by stimulating the release of histamine and/or nitric oxide. W e used intravital microscopy, clearance, and integrated optical intens ity (IOI), using FITC-dextran 150 (FITC-dx 150) as a tracer, to evalua te changes in microvascular permeability in the hamster cheek pouch. P oly-arg(n) at 1 mu M (topical) increased the clearance of FITC-dx 150 from 610 to 3240 nl/60 min/g. In contrast, 1 mu M polyglutamic acid (p oly-glu(n); and anionic peptide) did nor affect the clearance of FITC- dx 150 (605 nl/60 min/g), At 0.5 and 1.0 nM, poly-arg(n) 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 19 67 +/- 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-arg(n) at 1 n M 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 pol y-arg(n), as agonist, we assayed suffusate samples for their histamine concentration using a competitive enzyme immunoassay and found no det ectable histamine. Pyrilamine, an H-1 antagonist, did not inhibit the 0.5 nM poly-arg(n)-induced elevation in clearance of FITC-dx 150. We c onclude that (1) cationic peptides and MaBP increase microvascular per meability and (2) the increase in microvascular permeability produced by low concentrations of poly-arg(n) and by MaBP is independent of the release of histamine and does not require nitric oxide. (C) 1995 Acad emic Press, Inc.