Neutrophil Recruitment by Intradermally Injected Neutrophil Attractant/Activation Protein-1

Neutrophil attractant/activation protein-1 (NAP-l) is a recently described cytokine that attracts neutrophils, but not monocytes or eosinophils. This leukocyte specificity is not absolute, in that NAP-1 attracts basophils and small numbers of lymphocytes. Our purpose was to determine in vivo effects of NAP-1, and to compare them to the reported action of the complement attractant, C5a. Intradermal injection into normal human subjects of 40 μ1 of NAP-l, over a concentration range of 4 × 10-8 M to10-6 M, caused no symptoms or signs such as wheal-and-flare, itching, induration, or tenderness. However, biopsies of injection sites showed perivascular neutrophil infiltration as early as 30 rain, which increased at 1 and 3h. The mean number of neutrophils per mm2 of dermis for 15 biopsies taken 3h after intradermal injection of 2 × 10-7 M or 100-6 M NAP-1 was 164 ± 41; the response to saline or a NAP-1 inactive fragment was 5 or less. Intradermal NAP-1 did not cause basophil or lymphocyte infiltration. Consistent with the absence of a wheal-and-flare, acid toluidine blue-stained sections showed no evidence of mast cell degranulation, in contrast to previously reported results with C5a. Thus, the predominant response by human subjects to intradermal NAP-1 was neutrophil accumulation in proximity to dermal blood vessels.