A monoclonal antibody recognizing very late activation antigen-4 inhibits eosinophil accumulation in vivo.
Using an in vivo test system, the role of the beta 1 integrin very late activation antigen-4 (VLA-4) in eosinophil accumulation in allergic and nonallergic inflammatory reactions was investigated. Eosinophil infiltration and edema formation were measured as the local accumulation of intravenously injected 111In-labeled eosinophils and 125I-human serum albumin. The inflammatory reactions investigated were a passive cutaneous anaphylaxis (PCA) reaction and responses elicited by intradermal soluble inflammatory mediators (platelet-activating factor, leukotriene B4, C5a des Arg), arachidonic acid, and zymosan particles. The in vitro pretreatment of 111In-eosinophils with the anti-VLA-4 monoclonal antibody (mAb) HP1/2, which crossreacts with guinea pig eosinophils, suppressed eosinophil accumulation in all the inflammatory reactions investigated. Eosinophil accumulation was inhibited to the same extent when mAb HP1/2 was administered intravenously. It is interesting that HP1/2 had no effect on stimulated edema formation. These results suggest a role for VLA-4 in eosinophil accumulation in vivo and indicate a dissociation between the inflammatory events of eosinophil accumulation and edema formation.
Department of Applied Pharmacology, National Heart and Lung Institute, London, UK.
V B
VB
Weg
T J
TJ
Williams
R R
RR
Lobb
S
S
Nourshargh
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D004487:Edema / Q000276:immunology; D004804:Eosinophils / Q000276:immunology*; D006168:Guinea Pigs; D007249:Inflammation / Q000276:immunology; D007975:Leukotriene B4 / Q000494:pharmacology; D010323:Passive Cutaneous Anaphylaxis; D010972:Platelet Activating Factor / Q000494:pharmacology; D016029:Receptors, Very Late Antigen / Q000276:immunology*; D015054:Zymosan / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D010972:Platelet Activating Factor; D016029:Receptors, Very Late Antigen; D007975:Leukotriene B4; D015054:Zymosan