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(Journal of Leukocyte Biology. 2002;72:175-182.)
© 2002 by Society for Leukocyte Biology

Chemotactic activity of human blood leukocytes in plasma treated with EDTA: chemoattraction of neutrophils about monocytes is mediated by the generation of NAP-2

Stephen E. Malawista^*, Jo Van Damme, Joan I. Smallwood^* and Anne de Boisfleury Chevance

^* Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut;
Rega Institute for Medical Research, University of Leuven, Belgium; and
Centre d’Ecologie Cellulaire, Institut National de la Santé et de la Recherche Médicale, Hôpital de la Salpétrière, Paris, France

Correspondence: Dr. Stephen E. Malawista, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520-8031. E-mail: stephen.malawista{at}yale.edu

In slide preparations of human blood leukocytes in autologous plasma containing EDTA, many adherent monocytes are initially chemotactic for neutrophils (PMN). We have identified the chemotactic factor that they generate as neutrophil-activating peptide-2 (NAP-2), as evidenced by distraction of the gradient by authentic human NAP-2, the importance of platelets in the media, which elaborate the precursor of NAP-2, and suppression of the chemotactic response by serine protease inhibitors, which would block the monocyte-derived serine esterase that creates NAP-2 from its immediate precursor. Consistent with this conclusion is inhibition of the chemotactic response to monocytes by agents that block CXCR2, the receptor that NAP-2 uses. Later, when the monocyte moves from the center of chemoattraction, the activated PMN themselves, whose own chemotactic properties are enhanced in EDTA/plasma, appear to take over generation of the gradient, resulting in a prolonged ingress of PMN from outside the field ("second wave"). Chemoattraction by monocytes seems to be simply one way of stimulating the PMN, which, once activated, fail in EDTA/plasma to efficiently shut off their own chemoattraction for other PMN. We suggest that these exaggerated chemotactic effects are due to the loss of normal modulation by a regulatory factor(s) designed to keep the chemotactic response from getting out of hand—i.e., a tonic inhibitor of chemotaxis in plasma.

Key Words: locomotion • chemotaxis • chemokines

This article has been cited by other articles:

				S. E. Malawista, A. de Boisfleury Chevance, J. van Damme, and C. N. Serhan Tonic inhibition of chemotaxis in human plasma PNAS, November 18, 2008; 105(46): 17949 - 17954. [Abstract] [Full Text] [PDF]