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Induces Significant Recruitment of Neutrophils and Monocytes1
*
Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21224;
Catholic University School of Medicine, Seoul, Korea;
Pfizer, Inc., Groton, CT 06340; and
§
Mayo Clinic, Rochester, MN 55905
Macrophage inflammatory protein (MIP-1
), a member of the CC
chemokine subfamily, has been shown to attract T cells and monocytes in
vitro and to be expressed at sites of inflammation. Although the in
vitro activities of MIP-1 have been well documented, the in vivo
biological activities of MIP-1 in humans have not been studied. To
address this, we challenged human subjects by intradermal injection
with up to 1000 pmol of MIP-1 and performed biopsies 2, 10, and
24 h later. Although no acute cutaneous or systemic reactions were
noted, endothelial cell activation, as indicated by the expression of
E-selectin, was observed. In agreement with its in vitro activity,
monocyte, lymphocyte, and, to a lesser degree, eosinophil infiltration
was observed, peaking at 10–24 h. Surprisingly, in contrast to its
reported lack of in vitro neutrophil-stimulating activity, a rapid
infiltration of neutrophils was observed in vivo. This neutrophil
infiltration occurred as early as 2 h, preceding the appearance of
other cells, and peaked at 10 h. Interestingly, we found that
neutrophils in whole blood, but not after isolation, expressed CCR1 on
their cell surface. This CCR1 was thought to be functional as assessed
by neutrophil CD11b up-regulation following whole-blood MIP-1
stimulation. These studies substantiate the biological
effects of MIP-1 on monocytes and lymphocytes and uncover the
previously unrecognized activity of MIP-1 to induce neutrophil
infiltration and endothelial cell activation, underscoring the need to
evaluate chemokines in vivo in humans.
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