TY - JOUR
T1 - Cutaneous injection of human subjects with macrophage inflammatory protein-1α induces significant recruitment of neutrophils and monocytes
AU - Lee, Sang Chin
AU - Brummet, Mary E.
AU - Shahabuddin, Syed
AU - Woodworth, Thasia G.
AU - Georas, Steve N.
AU - Leiferman, Kristin M.
AU - Gilman, Steven C.
AU - Stellato, Cristiana
AU - Gladue, Ron P.
AU - Schleimer, Robert P.
AU - Beck, Lisa A.
PY - 2000/3/15
Y1 - 2000/3/15
N2 - Macrophage inflammatory protein (MIP-1α), 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- 1α have been well documented, the in vivo biological activities of MIP-1α in humans have not been studied. To address this, we challenged human subjects by intradermal injection with up to 1000 pmol of MIP-1α 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-1α stimulation. These studies substantiate the biological effects of MIP-1α on monocytes and lymphocytes and uncover the previously unrecognized activity of MIP-1α to induce neutrophil infiltration and endothelial cell activation, underscoring the need to evaluate chemokines in vivo in humans.
AB - Macrophage inflammatory protein (MIP-1α), 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- 1α have been well documented, the in vivo biological activities of MIP-1α in humans have not been studied. To address this, we challenged human subjects by intradermal injection with up to 1000 pmol of MIP-1α 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-1α stimulation. These studies substantiate the biological effects of MIP-1α on monocytes and lymphocytes and uncover the previously unrecognized activity of MIP-1α to induce neutrophil infiltration and endothelial cell activation, underscoring the need to evaluate chemokines in vivo in humans.
UR - http://www.scopus.com/inward/record.url?scp=0142100744&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0142100744&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.164.6.3392
DO - 10.4049/jimmunol.164.6.3392
M3 - Article
C2 - 10706735
AN - SCOPUS:0142100744
SN - 0022-1767
VL - 164
SP - 3392
EP - 3401
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -