Increased microvascular permeability in vivo in response to intradermal injection of neutrophil-activating protein (NAP-2) in rabbit skin.
Neutrophil-activating protein-2 (NAP-2), an NH2-terminally processed form of the platelet-release product beta thromboglobulin (beta TG), was purified to homogeneity from stimulated human blood leukocytes. In the presence of a vasodilator substance (PGE2, CGRP) picomolar (pmol/l) amounts of NAP-2 induced neutrophil accumulation and plasma leakage on intradermal injection in rabbit skin, whereas the longer forms, beta TG itself and connective tissue-activating peptide III (CTAP-III), had no such effect. NAP-2-induced increased in microvascular permeability was neutrophil dependent and fast in onset, with a half-life of 65 to 75 minutes, comparable to that previously reported for the structural-related neutrophil-activating protein-1/interleukin-8 (NAP-1/IL-8). However NAP-2 showed a lower potency in that more protein was needed to provoke skin reactivity. Nevertheless the finding that a platelet release product can elicit neutrophil-mediated inflammation further narrows the gap between thrombotic events and inflammatory disorders.
Van Osselaer
N
N
Division of Pharmacology, Faculty of Medicine, University of Antwerp (UIA), Belgium.
Van Damme
J
J
Rampart
M
M
Herman
A G
AG
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002199:Capillary Permeability; D002634:Chemotaxis, Leukocyte; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000473:pathology; D007271:Injections, Intradermal; D016209:Interleukin-8 / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D010455:Peptides / Q000494:pharmacology; D011817:Rabbits; D012709:Serum Albumin / Q000494:pharmacology; D012867:Skin / Q000098:blood supply*; D001620:beta-Thromboglobulin / Q000494:pharmacology
D016209:Interleukin-8; D010455:Peptides; D012709:Serum Albumin; D001620:beta-Thromboglobulin; C009862:connective tissue-activating peptide; D015740:Calcitonin Gene-Related Peptide