Analyses of microvascular permeability in response to mediators of immediate hypersensitivity.
Mediator-induced changes in microvascular permeability were studied in rodent skin. To monitor these changes, Evan's blue dye, iodinated rat albumin and IgG, and tritiated neutral dextran molecules having different molecular radii were used. After intradermal injections of serotonin, histamine, and bradykinin, the degree of radiolabeled tracer efflux was determined by measuring the extent of blueing and the level of radioactivity in skin biopsy specimens. Although the mediators varied in potency on a molar basis (serotonin greater than bradykinin greater than histamine), the efflux resulting from each was similar. Furthermore, kinetic studies revealed that each of these vasoactive agents caused a marked but transient increase in macromolecular permeability that lasted less than 30 minutes. To determine the pore size created and the effect of charge on the transudation of macromolecules into the interstitium, fractions of neutral [3H]dextrans with a known molecular size (average radii, 12 and 4.4 nm, respectively) were infused either singly or in combination with 125I-labeled rat albumin and/or IgG before intradermal injection of serotonin, histamine, bradykinin, or compound 48/80. Regardless of the mediator used, no differences could be demonstrated in macromolecular efflux, as indicated by either the molecular size of the charge of the tracer used. Thus, all mediators of immediate hypersensitivity reactions that were studied produce venular gaps greater than 12 nm in addition to displaying similar vasopermeable characteristics.
Keahey
T M
TM
Allergic Diseases Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
Indrisano
J
J
White
M V
MV
Kaliner
M A
MA
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects* / Q000502:physiology; D006632:Histamine / Q000494:pharmacology; D006969:Hypersensitivity, Immediate / Q000503:physiopathology*; D046911:Macromolecular Substances; D008970:Molecular Weight; D016062:Porosity / Q000187:drug effects; D051381:Rats; D012701:Serotonin / Q000494:pharmacology; D012867:Skin / Q000098:blood supply / Q000187:drug effects; D013997:Time Factors; D014699:Venules / Q000187:drug effects / Q000502:physiology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D046911:Macromolecular Substances; D012701:Serotonin; D003189:p-Methoxy-N-methylphenethylamine; D006632:Histamine; D001920:Bradykinin